Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Modulation of Electrical Properties by Ions, Hormones, and Drugs

Masayasu Hiraoka

10.1002/cphy.cp020116

Source: Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart

Originally published: 2002

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Effects of Electrolytes
1.1 Potassium Ions
1.2 Sodium Ions
1.3 Calcium and Other Divalent Cations
1.4 Chloride Ions
2 Effects of pH and Physical Factors
2.1 pH
2.2 Temperature
2.3 Stretch and Osmotic Pressure
3 Effects of Neurohormones and Their Receptor Stimulations
3.1 Adrenoceptor Agonists and Adrenergic Receptor Stimulation
3.2 Cholinergic Agonists and Cholinergic Receptor Stimulation
4 Effects of Circulatory Hormones and Autocrine/Paracrine Substances
4.1 Thyroid Hormones and Thyroid States
4.2 Insulin and Diabetes Mellitus
4.3 Effects of Adenosine and Adenine Nucleotides Through Purinergic Receptor Stimulation
4.4 Histamine and Histamine H2 Receptor Stimulation
4.5 Angiotensin II and Angiotensin Receptor Stimulation
4.6 Arginine Vasopressin and Vasopressinergic Receptor Stimulation
4.7 Endothelins
4.8 Atrial Natriuretic Peptide
4.9 Nitric Oxide
5 Effects of Drugs
5.1 Digitalis Glucosides
5.2 Potassium Channel Openers
Figure 1. Figure 1.

Effects of increasing [K+]o on action potentials and background membrane currents in atrial and ventricular myocytes. Action potentials and isochronal (5 s) current‐voltage relationships at [K+]o = 6 mM (filled circles) and 11 mM (open circles) in an atrial myocyte (A) and a ventricular myocyte (B) are shown. While action potential and the current‐voltage relationship were not much changed in A with increasing [K+]o from 6 to 11 mM, shortened action potential duration and a shift of I‐V relationship with crossover were evident in B. Tetrodotoxin (3 × 10−5 M) present throughout. In each cell, the holding potential was −50 mV. Vertical calibrations for insets in A and B are 20 mV; horizontal calibration is 50 msec for A and 100 ms for B.

Reproduced from Figure 11 in reference 289, with permission
Figure 2. Figure 2.

Activation of HERG current by extracellular K+ A–C: Currents elicited by 4 sec pulses to test potentials ranging from −50 to +20 mV in an oocyte bathed in modified ND96 solution containing 10 mM KCI (A) or 2 mM KCI (B) or 5 min after switching to ND96 solution with no added KCI (C). D: I‐V relationship for currents shown in A–C. E: HERG current amplitude varies as a function of [K+]o. Currents were measured at a test potential of +20 mV (n = 4–6). The solid line is a linear fit to data (IHERG = 189 + 37.5 [K+]o). Note that this relationship at lower and higher [K+]o would not be expected to be a linear function of [K+]o.

Reproduced from Figure 4 in reference 549 with permission
Figure 3. Figure 3.

[Ca2+]i induced potentiation and inhibition in the L‐type Ca2+ channel activity A: control; B: about 10 min after the bath solution was switched to Ca2+‐containing solution. Top panels show R340/380 indicating [Ca2+]i and bottom panels show NPO of the L‐type Ca2+ channel activity during each depolarizing pulse to O mV delivered at 1 Hz. C: unitary current records during the period indicated by bars in A and B. With increasing [Ca2+]i, channel activity was initially increased as shown in B‐b and C‐b. With further increase in [Ca2+]i above F340/380 ratio = 1.0, channel activity was now quickly inhibited (B‐c and C‐c). However, inhibitory effect was transient and with fluctuation of [Ca2+]i, channel activity was restored to the level which was still higher than the control B‐d and C‐d).

Reproduced from Figure 11 in reference 265 with permission
Figure 4. Figure 4.

Activation of ICl.Ca in different intracellular Ca2+ concentrations. A: ICl.Ca measured as 4,4′‐ddisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS)‐sensitive current traces at four different concentrations of Ca2+ in the pipette. The pipette solution contained 1 nM Ca2+ in a, 10 nM Ca2+ in b, 0.1 μ M Ca2+ in c, and 1 μM free Ca2+ in d. All experiments were done in the presence of 4 mM 4‐AP. Depolarizing pulses were applied from −60 mV to test potentials indicated to the left of each trace. B: current‐voltage relations of ICl.Ca. Data represent means ± S.E.M. •, 1 μM free Ca2+; ◯, 0.1 μM Ca2+; ▾, 10 nM Ca2+. Currents were normalized by dividing with total cell capacity.

Reproduced from Figure 6 in reference 342 with permission
Figure 5. Figure 5.

Current changes in response to inflation and deflation of sinoatrial node cell by applying positive and negative pressure through the recording electrode. A: chart record (10 mm/min) of current changes in response to the ramp clamp. The current traces indicated by a‐c are shown in B. The duration of inflation and deflation are indicated above the current trace. The pipette solution contained 24 mM C1− and the reversal potential for C1− (Ecl) was calculated to be −49 mV. The reversal potential of the stretch‐activated current was −48 mV (arrow in B), suggesting that the current activated in response to inflation of the cell is C1− elective.

Reproduced from Figure 2 in reference 229, with permission
Figure 6. Figure 6.

Effect of isoprenaline on the single Ca2+ channel currents. A: control; B: in the presence of 100 nM isoprenaline; C: after wash‐out of the drug. Depolarizing steps of 400 ms to −10 mV were applied repetitively from a holding potential (HP) of −80 mV at 2 Hz; 50 mM Ba2+ in the pipette. The number of steps was about 500 in each solution. a: typical current sweeps obtained after leakage current subtraction are given in the order of stimulation. Filtered at 1.5 kHz. b: the bottom traces: mean currents obtained by averaging the simulated openings from the total sweeps, including blank sweeps, on the same arbitrary scale. The ratio of the number of current‐containing sweeps to the total number of sweeps (availability) is given above each mean current.

Reproduced from Figure 1 in reference 489, with permission
Figure 7. Figure 7.

Effects of α1‐adrenergic stimulation on Ito single‐channel events. (I): A and B show a series of ten consecutive sweeps of single‐channel openings recorded under control conditions (A) and during bath exposure of the cell to 0.2 mM methoxamine (B). Ito single‐channel events were recorded following formation of the cell‐attached seal (about 100 GΩ); the patch membrane was held at −50 mV relative to the cell resting potential. Channel openings were elicited by 350 ms depolarizing pulses (150 mV) at a rate of 0.1 Hz. To remove the capacitative and leak currents from the single‐channel records, depolarizing pulses were applied at a rate of 2 Hz, and a total of ten to fifteen blank sweeps were averaged. This averaged record was then subtracted from the individual sweeps. C and D show the effect of methoxamine on the burst open probability of single Ito, channels (same patch as A and B). The burst open probability was determined by dividing the summed durations of individual openings present with a burst by the total duration of the given burst. A total of seventy to eighty bursts were recorded under control conditions (C) and in the presence of 0.2 mM methoxamine (D). (II): Effect of methoxamine on an ensemble average of the single‐channel events underlying Ito, from a cell‐attached patch containing several channels. Groups of thirty records were averaged before (C), during application of 0.2 mM methoxamine to the bath (M), and after wash‐out of methoxamine (W) from the bath. Depolarizing steps (+200 mV with respect to the cell resting potential; patch holding potential, −50 mV with respect to rest) were applied at a rate of 0.1 Hz.

Reproduced from Figures 4 and 5 in reference 53, with permission
Figure 8. Figure 8.

Activation of K+ channel by Ado and ACh requires intracellular GTP and blocked by IAP (islet‐activating protein or pertussis toxin). A: The cells were bathed in the internal solution. The concentration of agonists and the patch membrane potential are indicated at each current trace. At the arrow in each trace, the patch was excised from the cell, yielding the “inside‐out” patch. Activation of the channel was blocked in the “inside‐out” patches. During the period shown by the bar above each current trace, internal solution containing GTP 100 μM was perfused. Activation of the channel resumed abruptly by addition of GTP into the bath solution. B: The same patches as those in A. With GTP 100 μM present in the intracellular side of the membrane, channels remained activated. The A (active) protomer of IAP with NAD 1 mM was added in the internal solution containing GTP during the period indicated by the bar above each trace. Channel activation was gradually blocked by IAP within 1–3 min. The blocking effect of IAP was irreversible. When the A protomer was perfused in the absence of NAD, the activation of the channel was not blocked.

Reproduced from Figure 9 in reference 371 with permission
Figure 9. Figure 9.

Effects of ACh on SA node cells. Left: Effects of different ACh concentrations on the rate of spontaneous activity in an SA node myocyte. Activity was recorded in control Tyrode's solution (c) and during superfusion with ACh 0.01 μM (top) and 1 μM (bottom), as indicated. Right: Separation of the effects of ACh on Ii and IK.ACH. Two‐pulse protocols were applied every 3 sec during superfusion with various doses of ACh. The myocyte was superfused with normal Tyrode's solution (O, control) and with Tyrode's containing 0.01 (*), 0.1 (+), and 1 μM (x) ACh. In each case ACh superfusion was maintained until a steady‐state effect was achieved, typically 20 sec, and was followed by an appropriate washout period.

Reproduced from Figures 1 and 3 in reference 121, with permission
Figure 10. Figure 10.

Effect of isoproterenol (ISO), adenosine (Ado), and theophylline (Theo) on single‐channel Ca2+ current. A: Control; B: 100 nM ISO; C: 0.1 mM Ado and ISO; D: ISO, Ado, and 0.1 mM Theo. Traces labeled a are ten consecutive sweeps in order of depolarization sequence. Artifacts produced by capacitive transients were erased at the intervals indicated by the two dots. Traces labeled b are mean currents (m.c.) from all traces, including blanks. Mean currents were obtained by averaging the idealized openings and are shown on a constant arbitrary scale. About 1,000 times of 100 msec depolarization steps from the resting potential (R.P.) to R.P. +90 mV were applied repetitively at 2 Hz in each solution. Cutoff frequency was 1.5 kHz. Pipette solution contained 100 mM Ba2+, T.P.=test potential, H.P. = holding potential; Ps,=ratio of the number of channel currents containing sweeps to total number of sweeps.

Reproduced from Figure 1 in reference 337, with permission
Figure 11. Figure 11.

Desensitization and resensitization of the transient component of current evoked by external ATP. A: Current at — 130 mV during two applications of 200 μM ATP separated by 30 sec. While a transient current was lost in the second exposure to ATP due to desensitization, a maintained current response after the transient current was similarly evoked in the second exposure as in the first application. B: Time course of recovery from desensitization in two cells. In each trial, an initial 15‐sec application of 200 μM ATP was followed by a variable recovery time, and the extent of recovery was tested with a second application of ATP. Cells were allowed to recover for 6 min between trials. Filled circles: cell C78E. Open circles: cell C79B.

Reproduced from Figure 3 in reference 184 with permission
Figure 12. Figure 12.

Effect of endothelin‐1 (ET‐1) on the T‐type Ca2+ current ICa.T). A: A series of ICa.T were elicited by voltage steps to —30 mV in the control condition, 20 min after the addition of 10 nMET‐1, and 10 min after removal of ET‐1, and the tracings are superimposed. B: Peak current density‐voltage relations were plotted for ICa.T in the control condition (closed circles), 20 min after the addition of 10 nM ET‐1 (open reversed triangles), and 10 mins after the removal of ET‐1 (open squares) obtained from 11 cells. *P<0.05 and # P<0.01 for the control condition vs. ET‐1 and for ET‐1 vs. washout of ET‐1.

Reproduced from Figure 5 in reference 190 with permission
Figure 13. Figure 13.

The effect of strophanthidin on action potential and ICa when myocytes are impaled with BAPTA‐filled microelectrodes to increase Ca2+i buffering. A: The effect on the action potential of exposure to two different concentrations of strophanthidin. B: individual action potentials recorded at the times indicated in A. C: ICa recorded with the two‐pulse protocol before and at the end of strophanthidin exposure. D: The time course of the change in ICa during strophanthidin exposure and recovery.

Reproduced from Figure 8 in reference 400, with permission
Figure 14. Figure 14.

Effects of pinacidil on activation of ATP‐sensitive K+ channel currents recorded from an inside‐out patch membrane. A: Voltage‐dependent activation. Membrane potential [Vm (mV)] is indicated at the left of each trace. Left panel shows records taken during the control experiment with 0.5 mM ATP in the internal solution; right panel presents those with a solution containing 30 μM pinacidil and 2 mM ATP. The current direction is outward at positive voltages and inward at negative voltages. B a: Amplitude histograms (top panel) of the single‐channel current at Vm = −80 mV (left panel) and Vm = + 80 mV (right panel) obtained using the control solution containing 0.5 mM ATP. B b: Amplitude histograms (bottom panel) of the single‐channel current at Vm = 80 mV (left panel and Vm = +80 mV (right panel) obtained using solution containing 30 μM pinacidil and 2 mM ATP. Note that the current amplitude of the single channel is not changed by pinacidil. C: Current‐voltage relationship (I‐V) and the effect of pinacidil. Pinacidil does not change the conductance of this channel current.

Reproduced from Figure 2 in reference 160, with permission
Figure 15. Figure 15.

Concentration‐dependent effects of nicorandil on the SUR2A/Kir6.2 and SUR2B/Kir6.2 channels. Concentration‐dependent effects of nicorandil on the whole‐cell current of the SUR2A/Kir6.2 (a) and SUR2B/Kir6.2 channels (b) at −30 mV with 5.4 mM external K+. Arrowheads indicate the zero current level. The perfusion protocol is indicated above, c: Relationship between the concentration of nicorandil and the whole‐cell current of the SUR2A/Kir6.2 (open circles) and SUR2B/Kir6.2 channels (solid circles). The current amplitude induced by each concentration of nicorandil was normalized to the pinacidil (100 μM)‐induced current in the same cell. Each symbol and vertical lines indicate the mean and SE, respectively. The number of observations at each point was 5. The line is the fit of the data with the equation.Where the relative current is the current normalized to that induced by 100 μM pinacidil in the same cell; A is the maximum relative current induced by nicorandil; and [Nicorandil], the concentration of nicorandil. The values of A, K and nH were 1.05, 9.2 μM and 1.30, respectively.

Reproduced from Figure 3 in reference 587 with permission


Figure 1.

Effects of increasing [K+]o on action potentials and background membrane currents in atrial and ventricular myocytes. Action potentials and isochronal (5 s) current‐voltage relationships at [K+]o = 6 mM (filled circles) and 11 mM (open circles) in an atrial myocyte (A) and a ventricular myocyte (B) are shown. While action potential and the current‐voltage relationship were not much changed in A with increasing [K+]o from 6 to 11 mM, shortened action potential duration and a shift of I‐V relationship with crossover were evident in B. Tetrodotoxin (3 × 10−5 M) present throughout. In each cell, the holding potential was −50 mV. Vertical calibrations for insets in A and B are 20 mV; horizontal calibration is 50 msec for A and 100 ms for B.

Reproduced from Figure 11 in reference 289, with permission


Figure 2.

Activation of HERG current by extracellular K+ A–C: Currents elicited by 4 sec pulses to test potentials ranging from −50 to +20 mV in an oocyte bathed in modified ND96 solution containing 10 mM KCI (A) or 2 mM KCI (B) or 5 min after switching to ND96 solution with no added KCI (C). D: I‐V relationship for currents shown in A–C. E: HERG current amplitude varies as a function of [K+]o. Currents were measured at a test potential of +20 mV (n = 4–6). The solid line is a linear fit to data (IHERG = 189 + 37.5 [K+]o). Note that this relationship at lower and higher [K+]o would not be expected to be a linear function of [K+]o.

Reproduced from Figure 4 in reference 549 with permission


Figure 3.

[Ca2+]i induced potentiation and inhibition in the L‐type Ca2+ channel activity A: control; B: about 10 min after the bath solution was switched to Ca2+‐containing solution. Top panels show R340/380 indicating [Ca2+]i and bottom panels show NPO of the L‐type Ca2+ channel activity during each depolarizing pulse to O mV delivered at 1 Hz. C: unitary current records during the period indicated by bars in A and B. With increasing [Ca2+]i, channel activity was initially increased as shown in B‐b and C‐b. With further increase in [Ca2+]i above F340/380 ratio = 1.0, channel activity was now quickly inhibited (B‐c and C‐c). However, inhibitory effect was transient and with fluctuation of [Ca2+]i, channel activity was restored to the level which was still higher than the control B‐d and C‐d).

Reproduced from Figure 11 in reference 265 with permission


Figure 4.

Activation of ICl.Ca in different intracellular Ca2+ concentrations. A: ICl.Ca measured as 4,4′‐ddisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS)‐sensitive current traces at four different concentrations of Ca2+ in the pipette. The pipette solution contained 1 nM Ca2+ in a, 10 nM Ca2+ in b, 0.1 μ M Ca2+ in c, and 1 μM free Ca2+ in d. All experiments were done in the presence of 4 mM 4‐AP. Depolarizing pulses were applied from −60 mV to test potentials indicated to the left of each trace. B: current‐voltage relations of ICl.Ca. Data represent means ± S.E.M. •, 1 μM free Ca2+; ◯, 0.1 μM Ca2+; ▾, 10 nM Ca2+. Currents were normalized by dividing with total cell capacity.

Reproduced from Figure 6 in reference 342 with permission


Figure 5.

Current changes in response to inflation and deflation of sinoatrial node cell by applying positive and negative pressure through the recording electrode. A: chart record (10 mm/min) of current changes in response to the ramp clamp. The current traces indicated by a‐c are shown in B. The duration of inflation and deflation are indicated above the current trace. The pipette solution contained 24 mM C1− and the reversal potential for C1− (Ecl) was calculated to be −49 mV. The reversal potential of the stretch‐activated current was −48 mV (arrow in B), suggesting that the current activated in response to inflation of the cell is C1− elective.

Reproduced from Figure 2 in reference 229, with permission


Figure 6.

Effect of isoprenaline on the single Ca2+ channel currents. A: control; B: in the presence of 100 nM isoprenaline; C: after wash‐out of the drug. Depolarizing steps of 400 ms to −10 mV were applied repetitively from a holding potential (HP) of −80 mV at 2 Hz; 50 mM Ba2+ in the pipette. The number of steps was about 500 in each solution. a: typical current sweeps obtained after leakage current subtraction are given in the order of stimulation. Filtered at 1.5 kHz. b: the bottom traces: mean currents obtained by averaging the simulated openings from the total sweeps, including blank sweeps, on the same arbitrary scale. The ratio of the number of current‐containing sweeps to the total number of sweeps (availability) is given above each mean current.

Reproduced from Figure 1 in reference 489, with permission


Figure 7.

Effects of α1‐adrenergic stimulation on Ito single‐channel events. (I): A and B show a series of ten consecutive sweeps of single‐channel openings recorded under control conditions (A) and during bath exposure of the cell to 0.2 mM methoxamine (B). Ito single‐channel events were recorded following formation of the cell‐attached seal (about 100 GΩ); the patch membrane was held at −50 mV relative to the cell resting potential. Channel openings were elicited by 350 ms depolarizing pulses (150 mV) at a rate of 0.1 Hz. To remove the capacitative and leak currents from the single‐channel records, depolarizing pulses were applied at a rate of 2 Hz, and a total of ten to fifteen blank sweeps were averaged. This averaged record was then subtracted from the individual sweeps. C and D show the effect of methoxamine on the burst open probability of single Ito, channels (same patch as A and B). The burst open probability was determined by dividing the summed durations of individual openings present with a burst by the total duration of the given burst. A total of seventy to eighty bursts were recorded under control conditions (C) and in the presence of 0.2 mM methoxamine (D). (II): Effect of methoxamine on an ensemble average of the single‐channel events underlying Ito, from a cell‐attached patch containing several channels. Groups of thirty records were averaged before (C), during application of 0.2 mM methoxamine to the bath (M), and after wash‐out of methoxamine (W) from the bath. Depolarizing steps (+200 mV with respect to the cell resting potential; patch holding potential, −50 mV with respect to rest) were applied at a rate of 0.1 Hz.

Reproduced from Figures 4 and 5 in reference 53, with permission


Figure 8.

Activation of K+ channel by Ado and ACh requires intracellular GTP and blocked by IAP (islet‐activating protein or pertussis toxin). A: The cells were bathed in the internal solution. The concentration of agonists and the patch membrane potential are indicated at each current trace. At the arrow in each trace, the patch was excised from the cell, yielding the “inside‐out” patch. Activation of the channel was blocked in the “inside‐out” patches. During the period shown by the bar above each current trace, internal solution containing GTP 100 μM was perfused. Activation of the channel resumed abruptly by addition of GTP into the bath solution. B: The same patches as those in A. With GTP 100 μM present in the intracellular side of the membrane, channels remained activated. The A (active) protomer of IAP with NAD 1 mM was added in the internal solution containing GTP during the period indicated by the bar above each trace. Channel activation was gradually blocked by IAP within 1–3 min. The blocking effect of IAP was irreversible. When the A protomer was perfused in the absence of NAD, the activation of the channel was not blocked.

Reproduced from Figure 9 in reference 371 with permission


Figure 9.

Effects of ACh on SA node cells. Left: Effects of different ACh concentrations on the rate of spontaneous activity in an SA node myocyte. Activity was recorded in control Tyrode's solution (c) and during superfusion with ACh 0.01 μM (top) and 1 μM (bottom), as indicated. Right: Separation of the effects of ACh on Ii and IK.ACH. Two‐pulse protocols were applied every 3 sec during superfusion with various doses of ACh. The myocyte was superfused with normal Tyrode's solution (O, control) and with Tyrode's containing 0.01 (*), 0.1 (+), and 1 μM (x) ACh. In each case ACh superfusion was maintained until a steady‐state effect was achieved, typically 20 sec, and was followed by an appropriate washout period.

Reproduced from Figures 1 and 3 in reference 121, with permission


Figure 10.

Effect of isoproterenol (ISO), adenosine (Ado), and theophylline (Theo) on single‐channel Ca2+ current. A: Control; B: 100 nM ISO; C: 0.1 mM Ado and ISO; D: ISO, Ado, and 0.1 mM Theo. Traces labeled a are ten consecutive sweeps in order of depolarization sequence. Artifacts produced by capacitive transients were erased at the intervals indicated by the two dots. Traces labeled b are mean currents (m.c.) from all traces, including blanks. Mean currents were obtained by averaging the idealized openings and are shown on a constant arbitrary scale. About 1,000 times of 100 msec depolarization steps from the resting potential (R.P.) to R.P. +90 mV were applied repetitively at 2 Hz in each solution. Cutoff frequency was 1.5 kHz. Pipette solution contained 100 mM Ba2+, T.P.=test potential, H.P. = holding potential; Ps,=ratio of the number of channel currents containing sweeps to total number of sweeps.

Reproduced from Figure 1 in reference 337, with permission


Figure 11.

Desensitization and resensitization of the transient component of current evoked by external ATP. A: Current at — 130 mV during two applications of 200 μM ATP separated by 30 sec. While a transient current was lost in the second exposure to ATP due to desensitization, a maintained current response after the transient current was similarly evoked in the second exposure as in the first application. B: Time course of recovery from desensitization in two cells. In each trial, an initial 15‐sec application of 200 μM ATP was followed by a variable recovery time, and the extent of recovery was tested with a second application of ATP. Cells were allowed to recover for 6 min between trials. Filled circles: cell C78E. Open circles: cell C79B.

Reproduced from Figure 3 in reference 184 with permission


Figure 12.

Effect of endothelin‐1 (ET‐1) on the T‐type Ca2+ current ICa.T). A: A series of ICa.T were elicited by voltage steps to —30 mV in the control condition, 20 min after the addition of 10 nMET‐1, and 10 min after removal of ET‐1, and the tracings are superimposed. B: Peak current density‐voltage relations were plotted for ICa.T in the control condition (closed circles), 20 min after the addition of 10 nM ET‐1 (open reversed triangles), and 10 mins after the removal of ET‐1 (open squares) obtained from 11 cells. *P<0.05 and # P<0.01 for the control condition vs. ET‐1 and for ET‐1 vs. washout of ET‐1.

Reproduced from Figure 5 in reference 190 with permission


Figure 13.

The effect of strophanthidin on action potential and ICa when myocytes are impaled with BAPTA‐filled microelectrodes to increase Ca2+i buffering. A: The effect on the action potential of exposure to two different concentrations of strophanthidin. B: individual action potentials recorded at the times indicated in A. C: ICa recorded with the two‐pulse protocol before and at the end of strophanthidin exposure. D: The time course of the change in ICa during strophanthidin exposure and recovery.

Reproduced from Figure 8 in reference 400, with permission


Figure 14.

Effects of pinacidil on activation of ATP‐sensitive K+ channel currents recorded from an inside‐out patch membrane. A: Voltage‐dependent activation. Membrane potential [Vm (mV)] is indicated at the left of each trace. Left panel shows records taken during the control experiment with 0.5 mM ATP in the internal solution; right panel presents those with a solution containing 30 μM pinacidil and 2 mM ATP. The current direction is outward at positive voltages and inward at negative voltages. B a: Amplitude histograms (top panel) of the single‐channel current at Vm = −80 mV (left panel) and Vm = + 80 mV (right panel) obtained using the control solution containing 0.5 mM ATP. B b: Amplitude histograms (bottom panel) of the single‐channel current at Vm = 80 mV (left panel and Vm = +80 mV (right panel) obtained using solution containing 30 μM pinacidil and 2 mM ATP. Note that the current amplitude of the single channel is not changed by pinacidil. C: Current‐voltage relationship (I‐V) and the effect of pinacidil. Pinacidil does not change the conductance of this channel current.

Reproduced from Figure 2 in reference 160, with permission


Figure 15.

Concentration‐dependent effects of nicorandil on the SUR2A/Kir6.2 and SUR2B/Kir6.2 channels. Concentration‐dependent effects of nicorandil on the whole‐cell current of the SUR2A/Kir6.2 (a) and SUR2B/Kir6.2 channels (b) at −30 mV with 5.4 mM external K+. Arrowheads indicate the zero current level. The perfusion protocol is indicated above, c: Relationship between the concentration of nicorandil and the whole‐cell current of the SUR2A/Kir6.2 (open circles) and SUR2B/Kir6.2 channels (solid circles). The current amplitude induced by each concentration of nicorandil was normalized to the pinacidil (100 μM)‐induced current in the same cell. Each symbol and vertical lines indicate the mean and SE, respectively. The number of observations at each point was 5. The line is the fit of the data with the equation.Where the relative current is the current normalized to that induced by 100 μM pinacidil in the same cell; A is the maximum relative current induced by nicorandil; and [Nicorandil], the concentration of nicorandil. The values of A, K and nH were 1.05, 9.2 μM and 1.30, respectively.

Reproduced from Figure 3 in reference 587 with permission
References
 1. Agus, Z. S., I. D. Dukes, and M. Morad. Divalent cations modulate the transient outward current in rat ventricular myocytes. Am. J. Physiol. 261 (Cell Physiol. 30): C310–C318, 1991.
 2. Agus, Z. S., E. Kelepouris, I. Dukes, and M. Morad. Cytosolic magnesium modulates calcium channel activity in mammalian ventricular cells. Am. J. Physiol. 256 (Cell Physiol. 25): C452–C455, 1989.
 3. Agus, Z. S., and M. Morad. Modulation of cardiac ion channels by magnesium. Annu. Rev. Physiol. 53: 299–307, 1991.
 4. Allen, I. S., N. M. Cohen, R. S. Dhallan, S. T. Gaa, W. J. Lederer and T. B. Rogers. Angiotensin II increases spontaneous contractile frequency and stimulates calcium current in cultured neonatal rat heart myocytes: insights into the underlying biochemical mechanism. Circ. Res. 62: 524–534, 1988.
 5. Alvarez, J. L., K. Mongo, F. Scamps, and G. Vassort. Effects of purinergic stimulation on the Ca current in single frog cardiac cells. Pflugers Arch. 416: 189–195, 1990.
 6. Alvalez, J. L. and G. Vassort. Properties of the low threshold Ca current in single frog atrial cardiomyocytes. J. Gen. Physiol. 100: 519–545, 1992.
 7. Ananda‐Srivastava, M. B. and G. J. Trachte. Atrial natriuretic factor receptors and signal transduction mechanisms. Pharmacol. Rev. 45: 455–497, 1993.
 8. Anderson, M. E., A. P. Braun, H. Schulman, and B. A. Premack. Multifunctional Ca2+/calmodulin‐dependent protein kinase mediates Ca2+‐induced enhancement of the L‐type Ca2+ current in rabbit ventricular myocytes. Circ. Res. 75: 854–861, 1994.
 9. Antoni, H. and E. Oberdisse. Elektrophysiologische Untersuchungen uber die Barium‐induzierte Schrittmacher Aktivitat in der Arbeitmuskulatur des Saugertierherzens. Pflugers Arch. 284: 259–272, 1965.
 10. Antzelevitch, C., S. Sicouri, S. H. Litovsky, A. Lukas, S. C. Krishnan, J. M. DiDiergo, G. A. Gintant, and D. W. Liu. Heterogeneity within the ventricular wall—electrophysiology and pharmacology of epicardial, endocardial, and M‐cells. Circ. Res. 69: 1427–1449, 1991.
 11. Antzelevitch, C. S., A. Sicouri, V. V. Lukas, D. W. Nesterenko, W. Liu, and J. M. DiDiergo. Regional differences in the electro‐physiology of ventricular cells: physiological and clinical implications. In D. P. Zipes, and J. Jalife Cardiac Electrophysiology—From Cell to Bedside, edited by Philadelphia: W. B. Saunders Co., 1995: 228–245.
 12. Anumonwo, J. M. B., J. Horta, M. Delmar, S. M. Taffet, and J. Jalife. Proton and zinc effects on HERG current. Biophy. J. 77: 282–298, 1999.
 13. Apkon, M. and J. M. Nerbonne. α‐Adrenergic agonists selectively suppress voltage‐dependent K+ currents in rat ventricular myocytes. Proc. Natl. Acad. Sci. U.S.A. 85: 8756–8760, 1988.
 14. Apkon, M. and J. N. Nerbonne. Characterization of two distinct depolarization‐activated K+ currents in isolated adult rat ventricular myocytes. J. Gen. Physiol. 97: 973–1011, 1991.
 15. Arena, J. P. and R. S. Kass. Activation of ATP‐sensitive K channels in heart cells by pinacidil: dependence on ATP. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H2092–H2096, 1989.
 16. Arlock, P., and B. G. Katzung. Effects of sodium substrates on transient inward current and tension in guinea‐pig ventricular muscle. J. Physiol. (Lond.) 360: 105–120, 1985.
 17. Aronson, R. S. and P. F. Cranefield. The electrical activity of canine Purkinje fibers in sodium‐free, calcium‐rich solutions. J. Gen. Physiol. 61: 786–808, 1973.
 18. Ashcroft, F. M., and F. M. Gribble. Correlating structure and function in ATP‐sensitive K+ channels. Trends Neurosci. 21: 288–294, 1998.
 19. Attwell, D., I. Cohen, D. Eisner, M. Ohba, and C. Ojeda. The steady‐state TTX‐sensitive (‘window’) sodium current in Purkinje fibres. Pflugers Arch. 379: 137–142, 1979.
 20. Aulbach, F., A. Simm, S. Maier, H. Langenfeld, U. Walter, U. Kersting, and M. Kirstein. Insulin stimulates the L‐type Ca2+ current in rat cardiac myocytes. Cardiovasc. Res. 42: 113–120, 1999.
 21. Bahinski, H., A. C. Nairn, P. Greengard, and D. C. Gadsby. Chloride conductance regulated by cyclic AMP‐dependent protein kinase in cardiac myocytes. Nature 340: 718–721, 1989.
 22. Baker, K. M., G. W. Booz, and D. E. Dostal. Cardiac actions of angiotensin II: role of an intracardiac renin‐angiotensin system. Annu. Rev. Physiol. 54: 227–241, 1992.
 23. Balligand, J.‐L., R. A. Kelly, P. A. Marsden, T. W. Smith, and T. Michel. Control of cardiac muscle cell function by an endogeneous nitric oxide signaling system. Proc. Natl. Acad. Sci. U.S.A. 90: 347–351, 1993.
 24. Balligand, J.‐L., L. Kobzik, X. Han, D. M. Kaye, L. Belhassen, D. S. O'Hara, R. A. Kelly, W. Smith, and T. Michel. Nitric oxide‐dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J. Biol. Chem. 270: 14582–14586, 1995.
 25. Barhanin, J., F. Lesage, E. Guillemare, M. Fink, M. Lazdunski, and G. Romey. KvLQT1 and Isk (minK) proteins associate to form the Iks cardiac potassium current. Nature 384: 78–80, 1996.
 26. Barry, D. M. and J. M. Nerbonne. Myocardial potassium channels: electrophysiological and molecular diversity. Annu. Rev. Physiol. 58: 363–394, 1996.
 27. Bates, S. E. and A. M. Gurney. Ca2+‐dependent block and potentiation of L‐type calcium current in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 466: 345–365, 1993.
 28. Baukrowitz, T. U. Schulte, D. Oliver, S. Herlitze, T. Krauter, S. J. Tucker, J. P. Ruppersberg, and B. Falker. PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282: 1141–1144, 1998.
 29. Baumgarten, C. M. and H. A. Fozzard. Intracellular chloride activity in mammalian ventricular muscle. Am. J. Physiol. 241 (Cell Physiol. 10): C121–C129, 1981.
 30. Baumgarten, C. M., G. Isenberg, T. F. McDonald, and R. E. Ten Eick. Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibres during voltage clamp hyperpolarization. Experiments in sodium‐free bathing media. J. Gen. Physiol. 70: 149–169, 1977.
 31. Baumgarten, C. M., D. H. Singer, and H. A. Fozzard. Intra‐ and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria. Circ. Res. 54: 65–73, 1984.
 32. Bean, B. P., M. C. Norwicky, and R. W. Tsien. β‐Adrenergic modulation of calcium channels in frog ventricular heart cells. Nature 307: 371–375, 1984.
 33. Beaulieu, P., and C. Lambert. Peptide regulation of heart rate and interactions with autonomic nervous system. Cardiovasc. Res. 37: 578–585, 1998.
 34. Belardinelli, L., W. R. Giles, and A. West. Ionic mechanisms of adenosine actions in pacemaker cells from rabbit heart. J. Physiol. (Lond). 405: 615–633, 1988.
 35. Belardinelli, L. and G. Isenberg. Isolated atrial myocytes: Adenosine and acetylcholine increase potassium conductance. Am. J. Physiol. 244 (Heart Circ. Physiol. 13): H734–H737, 1983.
 36. Belardinelli, L., and G. Isenberg. Actions of adenosine and isoproterenol on isolated mammalian ventricular myocytes. Circ. Res. 53: 287–297, 1983.
 37. Belardinelli, L., J. Linden, and R. M. Berne. The cardiac effects of adenosine. Prog. Cardiovasc. Dis. 22: 73–97, 1989.
 38. Belardinelli, L., J. C. Shryock, Y. Song, D. Wang, and M. Srinivas. Ionic basis of the electrophysiological actions of adenosine on cardiomyocytes. FASEB J. 9: 359–365, 1995.
 39. Benfey, B. G. Minireview: function of myocardial α‐adrenoceptors. Life Sci. 46: 743–757, 1990.
 40. Benz, I., J. W. Herzig, and M. Kohlhardt. Opposite effects of angiotensin II and protein kinase C activator OAG on cardiac Na+ channels. J. Membr. Biol. 130: 183–190, 1992.
 41. Bescond, J., P. Bois, J. Petit‐Jacques, and J. Lenfant. Characterization of an angiotensin‐II‐activated chloride current in rabbit sino‐atrial node cells. J. Membr. Biol. 140: 153–161, 1994.
 42. Bielen, F. V., S. Bosteels, and F. Verdonck. Consequences of CO2 acidosis for transmembrane Na+ transport and membrane current in rabbit cardiac Purkinje fibres. J. Physiol. (Lond). 427: 325–345, 1990.
 43. Biermans, G., J. Vereecke, and E. Carmeliet. The mechanism of the inward‐rectifying K current during hyperpolarizing steps in guinea‐pig ventricular myocytes. Pflugers Arch. 410: 604–613, 1987.
 44. Binah, O., I. Rubenstein, and E. Gilat. Effects of thyroid hormone on the action potential and membrane current of guinea‐pig ventricular myocytes. Pflugers Arch. 409: 214–216, 1987.
 45. Bkaily, G., N. Perron, S. Wang, A. Sculptoreanu, D. Jacques, and D. Menard. Atrial natriuretic factor blocks the high‐threshold Ca2+ current and increases K+ current in fetal single ventricular cells. J. Mol. Cell. Cardiol. 25: 1305–1316, 1993.
 46. Bkaily, G., S. Wang, M. Bui, and D. Menard. ET‐1 stimulates Ca2+ currents in cardiac cells. J. Cardiovasc. Pharmacol. 26 (Suppl. 3): S293–S296, 1995.
 47. Blumenthal, E. M., and L. K. Kaczmarek. Modulation by cyclic AMP of a slowly activating potassium channel expressed in Xenopus oocytes. J. Neurosci. 12: 290–296, 1992.
 48. Bohm, M., B. Pieske, M. Ungerer and E. Erdmann. Characterization of A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts. Circ. Res. 65: 1201–1211, 1989.
 49. Bourinet, E., F. Fournier, P. Lory, P. Charnet, and J. Nargeot. Protein kinase C regulation of cardiac calcium channels expressed in Xenopus oocytes. Pflugers Arch. 421: 247–255, 1992.
 50. Bouron, A., N. M. Soldatov, and H. Reuter. The beta‐1 subunit is essential for modulation by protein kinase C of a human and a non‐human L‐type Ca2+ channel. FEBS Lett. 377: 159–162, 1995.
 51. Boutjdir, M., and N. El‐Sheriff. α 1‐Adrenoceptor regulation of delayed afterdepolarization and triggered activity in subendocardial Purkinje fibers surviving one day of myocardial infarction. J. Mol. Cell. Cardiol. 23: 83–90, 1991.
 52. Boyett, M. R. and A. Roberts. The fade of the response to acetylcholine at the rabbit isolated sino‐atrial node. J. Physiol. (Lond.) 393: 171–194, 1987.
 53. Brady, A. J. and J. W. Woodbury. The sodium‐potassium hypothesis as the basis of electrical activity in frog ventricle. J. Physiol. (Lond.) 154: 385–407, 1960.
 54. Braun, A. P., D. Fedida, R. B. Clark, and W. R. Giles. Intracellular mechanisms for α 1‐adrenergic regulation of the transient outward current in rabbit atrial myocytes. J. Physiol. (Lond.) 431: 689–712, 1990.
 55. Breitweisser, G. E. and G. Szabo. Uncoupling of cardiac muscarinic and β‐adrenergic receptors from ion channels by a guanine nucleotide analogue. Nature 317: 538–540, 1985.
 56. Brooks, C.McC. and H. H. Lu. The Sinoatrial Pacemaker of the Heart. Springfield, Illinois: Thomas, 1972.
 57. Brown, A. M. and L. Birnbaumer. Ionic channels and their regulation by G protein subunits. Annu. Rev. Physiol. 52: 197–213, 1990.
 58. Brown, J. H. and S. L. Brown. Agonists differentiate muscarinic receptors that inhibit cyclic AMP formation from those that stimulate phosphoinositide metabolism. J. Biol. Chem. 259: 3777–3781, 1984.
 59. Brown, R. H., I. Cohen, and D. Noble. The interactions of protons, calcium and potassium ions on cardiac Purkinje fibres. J. Physiol. (Lond.) 282: 345–352, 1978.
 60. Brown, G. L. and J. C. Eccles. The action of a single vagal volley on the rhythm of the heart beat. J. Physiol. (Lond.) 82: 211–240, 1934.
 61. Brown, H. F., D. DiFrancesco, and S. J. Noble. How does adrenaline accelerate the heart? Nature 280: 235–236, 1979.
 62. Brown, R. H. and D. Noble. Displacement of activation thresholds in cardiac muscle by protons and calcium ions. J. Physiol. (Lond.) 282: 333–343, 1978.
 63. Bruckner, R. and H. Scholz. Effects of α‐adrenoceptor stimulation with phenylephrine in the presence of propranolol on force of contraction, slow inward current and cyclic AMP content in the bovine heart. Br. J. Pharmacol. 82: 223–232, 1984.
 64. Brum, G., W. Osterrieder, and W. Trautwein. β‐Adrenergic increase in the calcium conductance of cardiac myocytes studied with the patch clamp. Pflugers Arch. 401: 111–118, 1984.
 65. Burnstock, G. A basis of distinguishing two types of purinergic receptors. In Cell Membrane Receptors for Drugs and Hormones, edited by L. Bolis and R. W. Straub. New York: Raven Press, 1978: 107–118.
 66. Burnstock, G. The past, present and future of purine nucleotides as signaling molecules. Neuropharmacology 36: 1127–1139, 1997.
 67. Busch, A. E., M. P. Kavanaugh, M. D. Varnum, J. P. Adelman, and R. A. North. Regulation by second messengers of the slowly activating voltage‐dependent potassium current expressed in Xenopus oocytes. J. Physiol. (Lond.) 450: 491–502, 1992.
 68. Bywater, R. A., G. D. Campbell, F. R. Edwards, and G. D. Hirst. Effects of vagal stimulation and applied acetylcholine on the arrested sinus venosus of the toad. J. Physiol. (Lond.) 425: 1–27, 1990.
 69. Cachelin, A. B., J. E. DePayer, S. Kokubun, and H. Reuter. Ca2+ channel modulation by 8‐bromocyclic AMP in cultured heart cells. Nature 304: 462–464, 1983.
 70. Capurro, N. and R. Levi. The heart as a target organ of cardiac anaphylaxis in vivo and in vitro. Circ. Res. 36: 520–528, 1975.
 71. Carmeliet, E. Chloride and Potassium Permeability in Cardiac Purkinje Fibres. Brussels. Presses Academiques Europeenes, 1961.
 72. Carmeliet, E. Introduction and removal of inward‐rectification in sheep cardiac Purkinje fibres. J. Physiol. (Lond.) 327: 285–308, 1982.
 73. Carmeliet, E. and K. Mubagwa. Characterization of the acetylcholine‐induced potassium current in rabbit cardiac Purkinje fibres. J. Physiol. (Lond.) 371: 219–237, 1986.
 74. Carmeliet, E. and K. Mubagwa. Desensitization of the acetylcholine‐induced increase of potassium conductance in rabbit cardiac Purkinje fibres. J. Physiol. (Lond.) 371: 239–255, 1986.
 75. Carmeliet, E. and J. Ramon. Electrophysiological effects of acetylcholine in sheep cardiac Purkinje fibres. Pflugers Arch. 387: 197–205, 1980.
 76. Carmeliet, E. and T. Saikawa. Shortening of action potential and reduction of pacemaker activity by lidocaine, quinidine, and procainamide in sheep cardiac Purkinje fibers. An effect on Na or K current? Circ. Res. 50: 257–272, 1982.
 77. Catterall, W. A. Modulation of sodium and calcium channels by protein phosphorylation and G proteins. Adv. Second Messenger Phosphoprotein Res. 31: 159–181, 1997.
 78. Caulfield, M. P., and N. J. Birdsall. International Union of Pharmacology. XVIL. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev. 50: 279–290, 1998.
 79. Cavalie, A., T. F. McDonald, D. Pelzer, and W. Trautwein. Temperature‐induced transitory and steady‐state changes in the calcium current of guinea pig ventricular myocytes. Pflugers Arch. 405: 294–296, 1985.
 80. Cerbai, E., U. Klockner, and G. Isenberg. Ca‐antagonistic effects of adenosine in guinea pig atrial cells. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H872–H878, 1988.
 81. Chang, F., J. Gao, C. Tromba, and D. DiFrancesco. Acetylcholine reverses effects of β‐agonists on pacemaker current in canine cardiac Purkinje fibers but has no direct action. Circ. Res. 66: 633–636, 1990.
 82. Chen, L., N. El‐Sherif, and M. Boutjdir. α 1‐Adrenergic activation inhibits β‐adrenergic stimulated unitary Ca2+ currents in cardiac ventricular myocytes. Circ. Res. 79: 184–193, 1996.
 83. Chen, S.‐A., M. S. Chang, B. N. Chiang, K. K. Cheng, and C. I. Lee. Electromechanical effects of angiotensin in human atrial tissues. J. Mol. Cell. Cardiol. 23: 483–493, 1991.
 84. Chen, X.‐H., I. Bezprozvanny, and R. W. Tsien. Molecular basis of proton block of L‐type Ca2+ channels. J. Gen. Physiol. 108: 363–374, 1996.
 85. Chesnais, J. M., E. Coraboeuf, M. P. Sauviat, and J. M. Vassort. Sensitivity to H, Li and Mg ions of the slow inward sodium current in frog atrial fibres. J. Mol. Cell. Cardiol. 7: 627–642, 1975.
 86. Christie, R., V. K. Sharma, and S. S. Sheu. Mechanism of extracellular ATP‐induced increase of cytosolic Ca2+ concentration in isolated rat ventricular myocytes. J. Physiol. (Lond.) 445: 365–388, 1992.
 87. Clapham, D. E., and E. Neer. New roles for G‐protein βγ‐dimers in transmembrane signaling. Nature 365: 403–406, 1993.
 88. Clemo, H. F., and C. M. Baumgarten. Swelling‐activated Gd+‐sensitive current and cell volume regulation in rabbit ventricular myocytes. J. Gen. Physiol. 110: 297–312, 1997.
 89. Clemo, H. F., C. M. Baumgarten, K. A. Ellenbogen, and B. S. Stambler. Atrial natriuretic peptide and cardiac electrophysiology: autonomic and direct effects. J. Cardiovasc. Electrophysiol. 7: 149–162, 1996.
 90. Clemo, H. F. and L. Belardinelli. Effect of adenosine on atrioventricular conduction. I. Site and characterization of adenosine action in the guinea‐pig atrioventricular node. Circ. Res. 59: 427–436, 1986.
 91. Clemo, H. F., B. S. Stambler, and C. M. Baumgarten. Persistent activation of a swelling‐activated cation current in ventricular myocytes from dogs with tachycardia‐induced congestive heart failure. Circ. Res. 83: 147–157, 1998.
 92. Clemo, H. F., B. S. Stambler, and C. M. Baumgarten. Swelling‐activated chloride A current is persistently activated in ventricular myocytes from dogs with tachycardia‐induced congestive heart failure. Circ. Res. 84: 157–165, 1999.
 93. Cole, W. C., C. D. McPherson, and D. Sontag. ATP‐regulated K+ channels protect the myocardium against ischemia/reperfusion damage. Circ. Res. 69: 571–581, 1991.
 94. Collier, M. L. and J. H. Hume. Unitary Ca− channels activated by cytoplasmic Ca2+ in canine ventricular myocytes. Circ. Res. 78: 936–944, 1996.
 95. Colquhoun, D., E. Neher, H. Reuter, and C. F. Stevens. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature 294: 752–754, 1981.
 96. Coraboeuf, E., E. Deroubaix, and A. Coulombe. Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am. J. Physiol. 236 (Heart Circ. Physiol. 5): H561–H567, 1979.
 97. Coraboeuf, E., E. Deroubaix, and A. Coulombe. Acidosis‐induced abnormal repolarization and repetitive activity in isolated dog Purkinje fibres. J. Physiol. (Paris) 76: 97–106, 1980.
 98. Cordeiro, J. M., K. W. Spitzer, and W. R. Giles. Repolarizing K+ currents in rabbit heart Purkinje cells. J. Physiol. (Lond.) 508: 811–823, 1998.
 99. Coulombe, A. and E. Coraboeuf. Large conductance chloride channels of new‐born rat cardiac myocytes are activated by hypotonic media. Pflugers Arch. 422: 143–150, 1992.
 100. Craelius, W., V. Chen, and N. El‐Sherif. Stretch activated ion channels in ventricular myocytes. Biosci. Rep. 8: 407–414, 1988.
 101. Cramb, G., R. Banks, E. L. Rugg, and J. F. Aiton. Actions of atrial natriuretic peptide (ANP) on cyclic nucleotide concentrations and phosphatidylinositol turnover in ventricular myocytes. Biochem. Biophys. Res. Commun. 148: 962–970, 1987.
 102. Cranefiel, P. F. The Conduction of the Cardiac Impulse: The Slow Response and Cardiac Arrhythmias. Mt. Kisco, NY: Futura Publishing Co., 1975.
 103. Cuevas, J., A. L. Bassett, J. S. Cameron, T. Furukawa, R. J. Myerburg, and S. Kimura. Effect of H+ on ATP‐regulated K+ channels in feline ventricular myocytes. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H755–H761, 1991.
 104. Damron, D. S., D. R. Van Wagoner, C. S. Moravec, and M. Bond. Arachidonic acid and endothelin potentiates Ca2+ transients in rat cardiac myocytes via inhibition of distinct K+ channels. J. Biol. Chem. 268: 27335–27344, 1993.
 105. Davies, N. W. Modulation of ATP‐sensitive K+ channels in skeletal muscle by intracellular protons. Nature 343: 375–377, 1990.
 106. Davis, L. D., P. R. Helmer, and F. Ballantyne III. Production of slow responses in canine cardiac Purkinje fibers exposed to reduced pH. J. Mol. Cell. Cardiol. 8: 61–76, 1976.
 107. Deal, K. K., S. K. England, and M. M. Tamkun. Molecular physiology of cardiac potassium channels. Physiol. Rev. 76: 49–67, 1996.
 108. Deck, K. A. Anderungen des Ruhepotentials und der Kabeleigenshaften von Purkinje‐Faden bei der Dehnung. Pflugers Arch. 280: 131–140, 1964.
 109. de Gaspo, M., A. Husain, W. Alexander, K. J. Katt, A. T. Chiu, M. Drew, T. Goodfriend, J. W. Harding, T. Inagami, and P. B. W. M. Tommermans. A proposed update of the nomenclature of angiotensin receptors. Hypertension 25: 924–927, 1995.
 110. DeHaan, R. L. and H. Gottlieb. The electrical activity of embryonic chick heart cells isolated in tissue culture singly or in interconnected cell sheets. J. Gen. Physiol. 52: 643–665, 1968.
 111. De Jongh, K. S., B. J. Murphy, A. A. Colvin, J. W. Hell, M. Takahashi, and W. A. Catterall. Specific phosphorylation of a site in the full‐length form of the alpha 1 subunit of the cardiac L‐type calcium channel by adenosine 3′, 5′‐cyclic monophosphate‐dependent protein kinase. Biochemistry 35: 10392–10402, 1996.
 112. Del Balzo, U., M. R. Rosen, G. Malfatto, L. M. Kaplan, and S. F. Steinberg. Specific α1‐adrenergic receptor subtypes modulate catecholamine‐induced increases and decreases in ventricular automaticity. Circ. Res. 67: 1535–1551, 1990.
 113. Del Castillo, J. and B. Katz. Production of membrane potential changes in the frog's heart by inhibitory nerve impulses. Nature 175: 1035, 1955.
 114. de Leon, M., Y. Yang, L. Jones, E. Perez‐Reyes, X. Wei, T. W. Song, T. P. Snutch, and D. T. Yue. Essential Ca2+‐binding motif for Ca2+‐sensitive inactivation of L‐type Ca2+ channels. Science 270: 1502–1506, 1995.
 115. Deleze, J. Perfusion of a strip of mammalian ventricle. Effects of K‐rich and Na‐deficient solutions on transmembrane potentials. Circ. Res. 7: 461–465, 1959.
 116. De Mello, W. C. Renin‐angiotensin system and cell communication in the failing heart. Hypertension 27: 1267–1272, 1996.
 117. De Mello, W. C. and B. F. Hoffmann. Potassium ions and electrical activity of specialized cardiac fibers. Am. J. Physiol. 199: 1125–1130, 1960.
 118. Denyer, J. and H. Brown. Pacemaking in rabbit isolated sinoatrial node cells during Cs+ block of the hyperpolarization‐activated current, if. J. Physiol. (Lond). 429: 401–409, 1990.
 119. Desilets, M. and C. M. Baumgarten. K+, Na+ and Cl− activities in ventricular myocytes isolated from rabbit heart. Am. J. Physiol. 251 (Cell Physiol. 20): C197–C208, 1986.
 120. DiFrancesco, D. A new interpretation of the pacemaker current in calf Purkinje fibres. J. Physiol. (Lond.) 314: 359–376, 1981.
 121. DiFrancesco, D. The contribution of the ‘pacemaker’ current (if) to generation of spontaneous activity in rabbit sino‐atrial node myocytes. J. Physiol. (Lond.) 434: 23–40, 1991.
 122. DiFrancesco, D. Pacemaker mechanisms in cardiac tissue. Annu. Rev. Physiol. 55: 451–467, 1993.
 123. DiFrancesco, D., P. Ducouret, and R. B. Robinson. Muscarinic modulation of cardiac rate at low acetylcholine concentrations. Science 243: 669–671, 1989,
 124. DiFrancesco, D., A. Ferroni, M. Mazzanti, and C. Tromba. Properties of the hyperpolarizing‐activated current (if) in cells isolated from the rabbit sino‐atrial node. J. Physiol. (Lond.) 377: 61–88, 1986.
 125. DiFrancesco, D., A. Ferroni, and S. Vinsentin. Barium‐induced blockade of the inward rectifier in calf Purkinje fibres. Pflugers Arch. 402: 446–453, 1984.
 126. DiFrancesco, D. and M. Mangoni. Modulation of single hyperpolarization‐activated channels (If) by cAMP in the rabbit sino‐atrial node. J. Physiol. (Lond.) 474: 473–482, 1994.
 127. DiFrancesco, D. and P. Tortora. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351: 45–147, 1991.
 128. DiFrancesco, D. and C. Tromba. Inhibition of the hyperpolarization‐activated current (If) induced by acetylcholine in rabbit sino‐atrial node myocytes. J. Physiol. (Lond.) 405: 477–491, 1988.
 129. DiFrancesco, D. and C. Tromba. Muscarinic control of the hyperpolarizing‐activated current if in rabbit sino‐atrial node myocytes. J. Physiol. (Lond.) 405: 493–510, 1988.
 130. Dirksen, R. T. and S. S. Sheu. Modulation of ventricular action potential by α1‐adrenoceptors and protein kinase C. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H907–H911, 1990.
 131. Doerr, T., R. Denger, and W. Trautwein. Calcium currents in single SA nodal cells of the rabbit heart studied with action potential clamp. Pflugers Arch. 413: 599–603, 1989.
 132. Dominguez, G. and H. A. Fozzard. Influence of extracellular K+ concentration on cable properties and excitability of sheep cardiac Purkinje fibers. Circ. Res. 26: 565–574, 1970.
 133. Dosemeci, A., R. S. Dhallan, N. M. Cohen, W. J. Lederer, and T. B. Rogers. Phorbol ester increases calcium current and simulates the effects of angiotensin II on cultured neonatal rat heart myocytes. Circ. Res. 62: 347–357, 1988.
 134. Dostal, D. E. and K. M. Baker. The cardiac renin‐angiotensin system. Conceptual, or a regulator of cardiac function? Circ. Res. 85: 643–650, 1999.
 135. Downey, J. M., and M. V. Cohen. Signal transduction in ischemic preconditioning. Adv. Exp. Med. Biol. 430: 39–55, 1997.
 136. Downey, J. M., G. S. Liu, and J. D. Thornton. Adenosine and the antiinfarct effects of preconditioning. Cardiovasc. Res. 27: 3–8, 1993.
 137. Duan, D., S. Cowley, B. Horowitz, and J. R. Hume. A serine residue in CIC‐3 links phosphorylation‐dephosphorylation to chloride channel regulation by cell volume. J. Gen. Physiol. 113: 57–70, 1999.
 138. Duan, D., B. Fermini, and S. Nattel. Sustained outward current observed after Ito1 inactivation in rabbit atrial myocytes is a novel C1− current. Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1967–H1971, 1992.
 139. Duan, D., B. Fermini, and S. Nattel. α‐Adrenergic control of volume‐regulated C1− currents in rabbit atrial myocytes. Circ. Res. 77: 379–393, 1995.
 140. Duan, D., and S. Nattel. Properties of single outwardly rectifying C1− channels in heart. Circ. Res. 75: 789–795, 1994.
 141. Duan, D., C. Winter, S. Cowley, J. R. Hume, and B. Horowitz. Molecular identification of a volume‐regulated chloride channel. Nature 390: 417–421, 1997.
 142. Duan, D., L. Ye, F. Britton, L. J. Miller, J. Yamazaki, B. Horowitz, and J. R. Hume. Purinoceptor‐coupled C1− channels in mouse heart: a novel, alternative pathway for CFTR regulation. J. Physiol. (Lond.) 521: 43–56, 1999.
 143. Duchatelle‐Gourdon, I., H. C. Hartzell, and A. A. Lagrutta. Modulation of the delayed rectifier potassium current in frog cardiomyocytes by β‐adrenergic agonists and magnesium. J. Physiol. (Lond.) 415: 251–274, 1989.
 144. Dudel, J. and W. Trautwein. Das Aktionpotential und Mechanogram des Herzmuskels unter dem Einfluss der Dehnung. Cardiologia 25: 344–362, 1954.
 145. Dudley, S. C. Jr., and C. M. Baumgarten. Bursting of cardiac sodium channels after exposure to 3,5,3′‐triiodo‐L‐thyronine. Circ. Res. 73: 301–313, 1993.
 146. Eckert, R. and E. Chad. Inactivation of calcium channels. Prog. Biophys. Mol. Biol. 44: 215–267, 1984.
 147. Eckert, R., J. Utz, W. Trautwein, and R. M. Mentzer, Jr. Involvement of intracellular Ca2+ release mechanism in adenosine‐induced cardiac Ca2+ current inhibition. Surgery 114: 334–342, 1993.
 148. Edwards, G. and A. H. Weston. The pharmacology of ATP‐sensitive potassium channels. Annu. Rev. Pharmacol. Toxicol. 33: 597–637, 1993.
 149. Egan, T. M., D. Noble, S. J. Noble, T. Powell, A. J. Spindler, and V. W. Twist. Sodium‐calcium exchange during the action potential in guinea‐pig ventricular cells. J. Physiol (Lond). 411: 639–661, 1989.
 150. Egan, T. M., D. Noble, S. J. Noble, T. Powell, V. W. Twist, and K. Yamaoka. On the mechanism of isoprenalin‐ and forskolin‐induced depolarization of single guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 400: 299–320, 1988.
 151. Ehara, T. and K. Ishihara. Anion channels activated by adrenaline in cardiac muscle. Nature 347: 284–286, 1990.
 152. Ehara, T., A. Noma, and K. Ono. Calcium‐activated nonselective cation channel in ventricular cells isolated from adult guinea‐pig hearts. J. Physiol. (Lond.) 403: 117–133, 1988.
 153. Eisner, D. A. and W. J. Lederer. Inotropic and arrhythmogenic effects of potassium‐depleted solutions on mammalian cardiac muscle. J. Physiol. (Lond.) 294: 255–277, 1979.
 154. Endou, M. and R. Levi. Histamine in the heart. Eur. J. Clin. Invest. 25 (Suppl. 1): 5–11, 1995.
 155. Ertl, R., U. Jahnel, H. Nawrath, E. Carmeliet, and J. Vereecke. Differential electrophysiological and inotropic effects of phenylephrine in atrial and ventricular heart muscle preparations from rat. N‐S Arch. Pharmacol. 344: 574–581, 1991.
 156. Escande, D., D. Thuringer, S. Le Guern, and I. Cavero. The potassium channel opener cromakalim (BRL 34915) activates ATP‐dependent K+ channels in isolated cardiac myocytes. Biochim. Biophys. Res. Commun. 154: 620–625, 1988.
 157. Ewart, H. S. and A. Klip. Hormonal regulation of the Na+–K+ ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am. J. Physiol. 269 (Cell Physiol. 38): C295–C311, 1995.
 158. Fan, Z., T. Furukawa, T. Sawanobori, J. C. Makielski, and M. Hiraoka. Cytoplasmic acidosis induces multiple conductance states in ATP‐sensitive potassium channels of cardiac myocytes. J. Membr. Biol. 136: 169–179, 1993.
 159. Fan, Z. and M. Hiraoka. Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes. Am. J. Physiol. 261 (Cell Physiol. 30): C23–C31, 1991.
 160. Fan, Z. and J. C. Makielski. Intracellular H+ and Ca2+ modulation of trypsin‐modified ATP‐sensitive K+ channels in rabbit ventricular myocytes. Circ. Res. 72: 715–722, 1993.
 161. Fan, Z. and J. C. Makielski. Anionic phospholipids activate ATP‐sensitive potassium channels. J. Biol. Chem. 272: 5388–5395, 1997.
 162. Fan, Z., K. Nakayama, and M. Hiraoka. Pinacidil activates the ATP‐sensitive K+ channel in inside‐out and cell‐attached patch membranes of guinea‐pig ventricular myocytes. Pflugers Arch. 415: 387–394, 1990.
 163. Fan, Z., K. Nakayama, and M. Hiraoka. Multiple actions of pinacidil on adenosine triphosphate‐sensitive potassium channels in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 430: 273–295, 1990.
 164. Fedida, D., A. P. Braun, and W. R. Giles. α 1‐Adrenoceptors reduce background K+ current in rabbit ventricular myocytes. J. Physiol. (Lond.) 441: 673–684, 1991.
 165. Fedida, D., A. P. Braun, and W. R. Giles. Changes in the rectifying potassium currents of atrial myocytes induced by α 1‐adrenoceptors in the presence and absence of acetylcholine. Pflugers Arch. 421: 431–439, 1992.
 166. Fedida, D., A. P. Braun, and W. R. Giles. α 1‐Adrenoceptors in myocardium: Functional aspects and transmembrane signaling mechanisms. Physiol. Rev. 73: 469–487, 1993.
 167. Fedida, D., D. Noble, and A. J. Spindler. Mechanism of the use dependence of Ca2+ current in guinea‐pig myocytes. J. Physiol. (Lond.) 405: 430–460, 1988.
 168. Fedida, D., Y. Shimoni, and W. R. Giles. α‐Adrenergic modulation of the transient outward current in rabbit atrial myocytes. J. Physiol. (Lond.) 423: 257–277, 1990.
 169. Fein, F. S., R. S. Aronson, C. Nordin, B. Miller‐Green, and E. H. Sonnenblick. Altered myocardial response to ouabain in diabetic rats: mechanisms and electrophysiology. J. Mol. Cell. Cardiol. 15: 769–784, 1983.
 170. Fein, F. S. and E. H. Sonnenblick. Diabetic cardiomyopathy. Prog. Cardiovasc. Dis. 27: 255–270, 1985.
 171. Ferguson, D. W., W. J. Berg, J. S. Sanders, P. J. Roach, J. S. Kempf, and M. G. Kienzle. Sympathoinhibitory responses to digitals glycosides in heart failure patients. Direct evidence from sympathetic neural recordings. Circulation 80: 65–77, 1989.
 172. Ferrier, G. R. Digitalis arrhythmias: role of oscillatory after‐potentials. Prog. Cardiovasc. Dis. 19: 459–474, 1977.
 173. Findlay, I. Effects of ADP upon the ATP‐sensitive K+ channel in rat ventricular myocytes. J. Membr. Biol. 101: 83–92, 1988.
 174. Findley, I. Calcium‐dependent inactivation of the ATP‐sensitive K+ channel of rat ventricular myocytes. Biochim. Biophys. Acta 943: 297–304, 1988.
 175. Fischmeister, R., M. Brocas‐Randolph, P. Lechene, J. A. Argibay, and G. Vassort. A dual effect of cardiac glycosides on Ca current in single cells of frog heart. Pflugers Arch. 406: 340–342, 1986.
 176. Fischmeister, R. and H. C. Hartzell. Mechanism of action of acetylcholine on calcium current in single cells from frog ventricle. J. Physiol. (Lond.) 376; 183–202, 1986.
 177. Fischmeister, R. and H. C. Hartzell. Cyclic guanosine 3′: 5′ monophosphate regulates the calcium current in single cells from frog ventricle. J. Physiol. (Lond.) 387: 453–472, 1987.
 178. Ford, A. P. D. W., T. J. Williams, D. R. Blue, and D. E. Clarke. α1‐Adrenoceptor classification: sharpening Occam's razor. Trends Pharmacol. Sci. 15: 167–170, 1994.
 179. Forrester, T. Release of ATP from heart. Ann. N.Y. Acad. Sci. 603: 335–351, 1990.
 180. Fosset, M., J. R. de Weille, R. D. Green, H. Schmid‐Antomarch, and M. Lazdunski. Antidiabetic sulphonylureas control action potential properties in heart cells via high affinity receptors that are linked to ATP‐dependent K+ channels. J. Biol. Chem. 263: 7933–7936, 1988.
 181. Fozzard, H. A., and D. A. Hanck. Structure and function of voltage‐dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol. Rev. 76: 887–926, 1996.
 182. Frankenhaeuser, B. and L. E. Moore. The effect of temperature on the sodium and potassium permeability changes in myelinated nerve fibers of Xenopus laevis. J. Physiol. (Lond.) 169: 431–437, 1963.
 183. Fredholm, B. B., M. P. Abbracchio, G. Burnstock, J. W. Daly, T. K. Harden, K. A. Jacobson, P. Leef, and M. Williams. VI. Nomenclature and classification of purinoceptors. Pharmacol. Rev. 46: 143–156, 1994.
 184. Fredholm, B. B., M. P. Abbracchio, G. Burnstock, G. R. Dubyak, T. K. Harden, K. A. Jacobson, U. Schwabe, and M. Williams. Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol. Sci. 18: 79–82, 1997.
 185. Freedberg, A. S., J. G. Papp, and E. M. Vaughan Williams. The effect of altered thyroid state on atrial intracellular potentials. J. Physiol. (Lond.) 207: 357–369, 1970.
 186. Friel, D. D. and B. P. Bean. Two ATP‐activated conductances in bullfrog atrial cells. J. Gen. Physiol. 91: 1–27, 1988.
 187. Friel, D. D. and B. P. Bean. Dual control by ATP and acetylcholine of inwardly rectifying K+ channels in bovine atrial cells. Pflugers Arch. 415: 651–657, 1990.
 188. Frohnwieser, B., L. Q. Chen, W. Schreibmyer, and R. G. Kallen. Modulation of the human cardiac sodium channel alpha‐subunit by cAMP‐dependent protein kinase and the responsible sequence domain. J. Physiol. (Lond.) 498: 309–318, 1997.
 189. Fry, C. H. and P. A. Pool‐Wilson. Effects of acid‐base changes on excitation‐contraction coupling in guinea‐pig and rabbit cardiac ventricular muscle. J. Physiol. (Lond.) 313: 141–160, 1981.
 190. Fu, C., A. Pleumsamran, U. Oh, and D. Kim. Different properties of the atrial G protein‐gated K+ channels activated by extracellular ATP and adenosine. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1349–H1358, 1995.
 191. Furukawa, T., Z. Fan, T. Sawanobori, and M. Hiraoka. Modification of the adenosine 5′‐trophosphate‐sensitive K+ channel by trypsin in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 466: 707–726, 1993.
 192. Furukawa, T., H. Ito, J. Nitta, M. Tsujino, S. Adachi, M. Hiroe, F. Marumo, T. Sawanobori, and M. Hiraoka. Endothelin‐1 enhances calcium entry through T‐type calcium channels in cultured neonatal rat ventricular myocytes. Circ. Res. 71: 1242–1253, 1992.
 193. Furukawa, T., L. Virag, N. Furukawa, T. Sawanobori, and M. Hiraoka. Mechanism for reactivation of the ATP‐sensitive K+ channel by MgATP complexes in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 479: 95–107, 1994.
 194. Furukawa, T., T. Yamane, T. Terai, Y. Katayama, and M. Hiraoka. Functional linkage of the cardiac ATP‐sensitive K+ channel to the actin cytoskeleton. Pflugers Arch. 431: 504–512, 1996.
 195. Gadsby, D. C. The Na/K pump of cardiac cells. Annu. Rev. Biophys. Bioeng. 13: 373–398, 1984.
 196. Gadsby, D. C. and A. C. Nairn. Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis. Physiol. Rev. 79: S77–S107, 1999.
 197. Gadsby, D. C., A. L. Wit, and P. F. Cranefield. The effects of acetylcholine on the electrical activity of canine cardiac Purkinje fibers. Circ. Res. 43: 29–35, 1978.
 198. Gallo, M. P., G. Alloatti, C. Eva, A. Oberto, and R. C. Levi. M1 muscarinic receptors increase calcium current and phosphoinositide turnover in guinea‐pig ventricular cardiocytes. J. Physiol. (Lond.) 471: 41–60, 1993.
 199. Gao, J., I. S. Cohen, R. T. Mathias, and G. J. Baldo. Regulation of the beta‐stimulation of the Na+‐K+ pump current in guinea‐pig ventricular myocytes by a cAMP‐dependent PKA pathway. J. Physiol. (Lond.) 477: 373–380, 1994.
 200. Gao, T., A. Yatani, M. L. Dell'Acqua, H. Sako, S. A. Green, N. Dascal, J. D. Scott, and M. M. Hosey. cAMP‐dependent regulation of cardiac L‐type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits. Neuron 19: 185–196, 1997.
 201. Garlid, K. D., P. Paucek, V. Yarov‐Yaronoy, H. N. Murray, R. B. Darbenzio, A. J. D'Alonzo, N. J. Lodge, M. A. Smith, and G. J. Grover. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP‐sensitive K+ channels: possible mechanism of cardioprotection. Circ. Res. 81: 1072–1082, 1997.
 202. Gauthier, C., G. Tavernier, F. Carpentier, D. Lagin, and H. Le Marec. Functional β3‐adrenoceptor in the human heart. J. Clin. Invest. 98: 556–562, 1996.
 203. George, W. J., L. J. Ignarro, R. J. Paddock, L. White, and P. J. Kadowitz. Oppositional effects of acetylcholine and isoproterenol on isometric tension and cyclic nucleotide concentrations in rabbit atria. J. Cyclic Nucleotide Res. 1: 339–347, 1975.
 204. Giles, W. R. and Y. Imaizumi. Comparison of potassium currents in rabbit atrial and ventricular cells. J. Physiol. (Lond.) 405: 123–145, 1988.
 205. Giles, W. R., T. Nakajima, K. Ono, and E. F. Shibata. Modulation of the delayed rectifier K+ current by isoprenaline in bullfrog atrial myocytes. J. Physiol. (Lond.) 415: 233–249, 1989.
 206. Giles, G. R. and A. C. G. Van Ginneken. A transient outward current in isolated cells from the crista terminalis of rabbit heart. J. Physiol. (Lond.) 368: 243–264, 1985.
 207. Gillis, R. A. and J. A. Quest. The role of the central nervous system in the cardiovascular effects of digitalis. Pharmacol. Rev. 31: 19–97, 1980.
 208. Gintant, G. A., N. B. Datyner, and I. S. Cohen. Slow inactivation of a tetrodotoxin‐sensitive current in canine cardiac Purkinje fibres. Biophys. J. 45: 509–512, 1984.
 209. Gintant, G. A. and D. W. Liu. β‐Adrenergic modulation of fast inward sodium current in canine myocardium: syncytial preparations versus isolated myocytes. Circ. Res. 70: 844–850, 1992.
 210. Giotti, A., F. Ledda, and P. F. Mannaioni. Effects of noradrenaline and isoprenaline, in combination with α‐ and β‐receptor blocking substances on the action potential of cardiac Purkinje fibres. J. Physiol. (Lond.) 229: 99–113, 1973.
 211. Gisbert, M. P. and R. Fischmeister. Atrial natriuretic factor regulates the calcium current in frog isolated cardiac cells. Circ. Res. 62: 660–667, 1988.
 212. Glitsch, H. G. Electrogenic Na pumping in the heart. Annu. Rev. Physiol. 44: 389–400, 1982.
 213. Glitsch, H. G. and L. Pott. Effects of acetylcholine and parasympathetic nerve stimulation on membrane potential in quiescent guinea‐pig atria. J. Physiol. (Lond.) 279: 655–668, 1978.
 214. Gordon, J. L. Extracellular ATP: effects, sources and fate. Biochem. J. 233: 309–319, 1986.
 215. Graham, R. M., Perez, D. M., J. Hwa, and M. T. Piascik. α1‐Adrenergic receptor subtypes. Molecular structure, function and signaling. Circ. Res. 78: 737–749, 1996.
 216. Grant, A. O., L. J. Strauss, A. G. Wallace, and H. C. Strauss. The influence of pH on the electrophysiological effects of lidocaine in guinea‐pig ventricular myocardium. Circ. Res. 47: 542–550, 1980.
 217. Gross, G. J. ATP‐sensitive potassium channels and myocardial preconditioning. Basic Res. Cardiol. 90: 85–88, 1995.
 218. Grover, G. L., J. R. McCullough, D. E. Henry, M. L. Condor, and P. G. Sleph. Anti‐ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker glyburide. J. Pharmacol. Exp. Ther. 251: 98–104, 1989.
 219. Grover, G. L., P. G. Sleph, and S. Dzwonczyk. Role of ATP‐sensitive K+ channels in mediating preconditioning in the dog and their possible interaction with adenosine A1 receptors. Circulation 86: 1310–1316, 1992.
 220. Guo, J., K. Ono, and A. Noma. A sustained inward current activated at the diastolic potential range in rabbit sino‐atrial node cells. J. Physiol. (Lond.) 483: 1–13, 1995.
 221. Gupta, R. C., Neumann, J., P. Boknik, and A. M. Watanabe. M2‐specific muscarinic cholinergic receptor‐mediated inhibition of cardiac regulatory protein phosphorylation. Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H1138–H1144, 1994.
 222. Gurney, A. M., P. Charnet, J. M. Pye, and J. Nargeot. Augmentation of cardiac calcium current by flash photolysis of intracellular caged‐Ca2+ molecules. Nature 341: 65–68, 1989.
 223. Gurwitz, D. and M. Sokolovsky. Dual pathways in muscarinic receptor stimulation of phosphoinositide hydrolysis. Biochemistry 26: 633–638, 1987.
 224. Haase, H., S. Bartel, P. Karczewski, I. Morano, and E. G. Krause. In‐vivo phosphorylation of the cardiac L‐type calcium channel beta‐subunit in response to catecholamines. Mol. Cell. Biochem. 163–164: 99–106, 1996.
 225. Habuchi, Y., L‐L. Lu, J. Morikawa, and M. Yoshimura. Angiotensin II inhibition of L‐type Ca2+ current in sinoatrial node cells of rabbits. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1053–H1060, 1995.
 226. Habuchi, Y., H. Tanaka, T. Furukawa, Y. Tsujimoto, H. Takahashi, and M. Yoshimura. Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H345–H354, 1992.
 227. Haga, T., K. Haga, and K. Kameyama. G protein‐coupled receptor kinases. J. Neurochem. 63: 400–412, 1994.
 228. Hagiwara, N. and H. Irisawa. Modulation by intracellular Ca2+ of the hyperpolarization‐activated inward current in rabbit single sinoatrial node cells. J. Physiol. (Lond.) 409: 121–141, 1989.
 229. Hagiwara, N., H. Irisawa, and M. Kameyama. Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino‐atrial node cells. J. Physiol. (Lond.) 395: 233–253, 1988.
 230. Hagiwara, N., H. Irisawa, H. Kasanuki, and S. Hosoda. Background current in sino‐atrial node cells of the rabbit heart. J. Physiol. (Lond.) 448: 53–72, 1992.
 231. Hagiwara, N., H. Masuda, M. Shoda, and H. Irisawa. Stretch‐activated anion currents of rabbit cardiac myocytes. J. Physiol. (Lond.) 456: 285–302, 1992.
 232. Hagiwara, S., S. Miyazaki, W. Moody, and J. Patlak. Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J. Physiol. (Lond.) 67: 621–638, 1978.
 233. Hall, S. K., J. Zhang, and M. Lieberman. Cyclic AMP prevents activation of a swelling‐induced chloride‐sensitive conductance in chick heart cell. J. Physiol. (Lond.) 488: 359–369, 1995.
 234. Han, X. and G. R. Ferrier. Ionic mechanisms of transient inward current in the absence of Na+‐Ca2+ exchange in rabbit cardiac Purkinje fibres. J. Physiol. (Lond.) 456: 19–38, 1992.
 235. Han, X., L. Kobzik, J.‐L. Balligand, R. A. Kelly, and T. W. Smith. Nitric oxide synthase (NOS3)‐mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells. Circ. Res. 78: 998–1008, 1996.
 236. Han, X., Y. Schimoni, and W. R. Giles. An obligatory role for nitric oxide in autonomic control of mammalian heart rate. J. Physiol. (Lond.) 476: 309–314, 1994.
 237. Han, X., Y. Schimoni, and W. R. Giles. A cellular mechanism for nitric oxide–mediated cholinergic control of mammarian heart rate. J. Gen. Physiol. 106: 45–65, 1995.
 238. Hancock, A. A., A. L. DeLean, and R. J. Refkowitz. Quantitative resolution of beta‐adrenergic subtypes by selective ligand binding: application of a computerized model fitting technique. Mol. Pharmacol. 16: 1–9, 1980.
 239. Hancox, J. C. and A. J. Levi. L‐type calcium current in rod‐ and spindle‐shaped myocytes isolated from rabbit atrioventricular node. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): H1670–H1680, 1994.
 240. Hancox, J. C. and A. J. Levi. Actions of the digitalis analogue strophanthidin on action potentials and L‐type calcium current in single cells isolated from the atrioventricular node. Br. J. Pharmacol. 1118: 1447–1454, 1996.
 241. Hardley, R. W. and W. J. Lederer. Ca2+ and voltage inactivate Ca2+ channels through independent mechanisms. J. Physiol. (Lond.) 444: 257–268, 1991.
 242. Harris, D. R., W. L. Green, and W. Craelius. Acute thyroid hormone promotes slow inactivation of sodium current in neonatal cardiac myocytes. Biochim. Biophys. Acta 1095: 175–181, 1991.
 243. Harrison, S. M., E. McCall, and M. R. Boyett. The relationship between contraction and intracellular sodium in rat and guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 449: 517–550, 1992.
 244. Hartzell, H. C. Adenosine receptors in frog sinus venosus: slow inhibitory potentials produced by adenine compounds and acetylcholine. J. Physiol. (Lond.) 293: 23–49, 1979.
 245. Hartzell, H. C. Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systems. Prog. Biophys. Mol. Biol. 52: 165–247, 1988.
 246. Hartzell, H. C. and R. Fischmeister. Opposite effects of cyclic GMP and cyclic AMP on Ca2+ current in single heart cells. Nature 323: 273–275, 1986.
 247. Hartzell, H. C. and R. Fischmeister. Direct regulation of cardiac Ca2+ channels by G protein: neither proven nor necessary? Trends Pharmacol. Sci. 13: 380–385, 1992.
 248. Hartzell, H. C., Y. Hirayama, and J. Petit‐Jacque. Effects of protein phosphatase and kinase inhibitors on the cardiac L‐type Ca current suggest two sites are phosphorylated by protein kinase A and another protein kinase. J. Gen. Physiol. 106: 393–414, 1995.
 249. Harvey, R. D., C. D. Clarck, and J. R. Hume. Chloride current in mammalian cardiac myocytes—novel mechanism for autonomic regulation of action potential duration and resting membrane potential. J. Gen. Physiol. 95: 1077–1102, 1990.
 250. Harvey, R. D. and J. R. Hume. Autonomic regulation of a chloride current in heart. Science 244: 983–985, 1989.
 251. Harvey, R. D. and J. R. Hume. Autonomic regulation of delayed rectifier K+ current in mammarian heart involves G protein. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H818–H823, 1989.
 252. Harvey, R. D. and J. R. Hume. Histamine activates the chloride current in cardiac ventricular myocytes. J. Cardiovasc. Electrophysiol. 1: 309–317, 1990.
 253. Hawthorn, M. H., P. Gengo, X‐Y. Wei, A. Rutledge, J. F. Moran, S. Gallant, and D. J. Triggle. Effect of thyroid status on β‐adrenoceptors and calcium channels in rat cardiac and vascular tissue. N‐S. Arch. Pharmacol. 337: 539–544, 1988.
 254. Hazeki, O. and M. Ui. Modification of islet‐activating protein of receptor‐mediated regulation of cyclic AMP accumulation in isolated rat heart cells. J. Biol. Chem. 256: 2856–2862, 1981.
 255. Heidebuchel, H., J. Vereecke, and E. Carmeliet. Atrial membranes contain nucleotide diphosphate kinase (NDPK) activity: its role in regulation of muscarinic K+ channels. J. Cardiovasc. Electrophysiol. 14: 1721–1727, 1991.
 256. Herzig, J. W. and M. Kohlhardt. Na+ channel blockade by cyclic AMP and other 6‐aminopurines in neonatal rat heart. J. Membr. Biol. 119: 163–170, 1991.
 257. Hescheler, J., M. Kameyama, and W. Trautwein. On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflugers Arch. 407: 182–189, 1986.
 258. Hescheler, J., H. Nawrath, M. Tang, and W. Trautwein. Adrenoceptor‐mediated changes of excitation and contraction in ventricular heart muscle from guinea‐pigs and rabbits. J. Physiol. (Lond.) 397: 657–670, 1988.
 259. Hescheler, J., M. Tang, B. Jastorff, and W. Trautwein. On the mechanism of histamine induced enhancement of the cardiac Ca2+ current. Pflugers Arch. 410: 23–29, 1987.
 260. Hess, P., J. B. Lansman, and R. W. Tsien. Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells. J. Gen. Physiol. 88: 293–319, 1986.
 261. Heyndrickx, G. R., D. H. Boettcher, and S. F. Vatner. Effects of angiotensin, vasopressin and methoxamine on cardiac function and blood flow distribution in conscious dogs. Am. J. Physiol. 231: 1579–1587, 1976.
 262. Hilgemann, D. W. and Ball, R. Regulation of cardiac Na+, Ca2+ exchange and KATP potassium channels. Science 273: 956–959, 1996.
 263. Hill, S. J., C. R. Ganellin, H. Timmerman, J‐C. Schwartz, N. P. Shankly, J. M. Young, W. Schunack, R. Levi, and H. Haas. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol. Rev. 49: 252–278, 1995.
 264. Hino, N. and R. Ochi. Effects of acetylcholine on membrane currents in guinea‐pig papillary muscle. J. Physiol. (Lond.) 307: 183–197, 1980.
 265. Hirano, Y., S. Abe, T. Sawanobori, and M. Hiraoka. External ATP‐induced changes in [Ca2+]i and membrane currents in mammalian atrial myocytes. Am. J. Physiol. 260 (Cell Physiol. 29) C673–C680, 1991.
 266. Hirano, Y. and M. Hiraoka. Barium‐induced automatic activity in isolated ventricular myocytes from guinea‐pig hearts. J. Physiol. (Lond.) 359: 455–472, 1988.
 267. Hirano, Y. and M. Hiraoka. Dual modulation of unitary L‐type Ca2+ channel currents by [Ca2+]i in fura‐2‐loaded guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 480: 449–463, 1994.
 268. Hirano, Y., K. Suzuki, N. Yamawake, and M. Hiraoka. Multiple kinetic effects of β‐adrenergic stimulation on single cardiac L‐type Ca channels. Am. J. Physiol. 266 (Cell Physiol. 35): C1714–C1721, 1994.
 269. Hirano, Y., T. Yoshinaga, T. Niidome, K. Katayama, and M. Hiraoka. Modulation by dihydropyridines and protein kinases of the recombinant cardiac L‐type Ca channel with multiple unitary current amplitudes. Receptors Channels 4: 93–104, 1996.
 270. Hiraoka, M. and Z. Fan. Activation of ATP‐sensitive outward K+ current by nicorandil (2‐nicotinamidoethyl nitrate) in isolated ventricular myocytes. J. Pharmacol. Exp. Ther. 250: 278–285, 1989.
 271. Hiraoka, M. and S. Kawano. Calcium‐sensitive and insensitive transient outward current in rabbit ventricular myocytes. J. Physiol. (Lond.) 410: 187–212, 1989.
 272. Hiraoka, M., S. Kawano, Y. Hirano, and T. Furukawa. Role of chloride currents in action potential characteristics and arrhythmias. Cardiovasc. Res. 40: 23–33, 1998.
 273. Hiraoka, M. and Y. Okamoto. Two types of abnormal automaticity in canine ventricular tissues. N‐S. Arch. Pharmacol. 317: 339–344, 1981.
 274. Hiraoka, M., Y. Okamoto, and T. Sano. Oscillatory afterpotentials in dog ventricular muscle fibers. Circ. Res. 48: 510–518, 1981.
 275. Hiraoka, M., A. Sunami, Z. Fan, and T. Sawanobori. Multiple ionic mechanisms of early afterdepolarizations in isolated ventricular myocytes from guine‐pig hearts. Ann. N.Y. Acad. Med. 644: 33–47, 1992.
 276. Ho, W.‐K., Y. E. Earm, S. H. Lee, H. F. Brown, and D. Noble. Voltage‐ and time‐dependent block of delayed rectifier K+ current in rabbit sino‐atrial node cells by external Ca2+ and Mg2+. J. Physiol. (Lond.) 494: 727–742, 1996.
 277. Ho, W.‐K., I. Kim, C. O. Lee, and Y. E. Earm. Voltage‐dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+. J. Physiol. (Lond.) 507: 631–638, 1998.
 278. Ho, W.‐K., I. Kim, C. H. Lee, J. B. Youm, S. H. Lee, and Y. E. Earm. Blockade of HERG channels expressed in Xenopus laevis oocytes by external divalent cations. Biophys. J. 76: 1959–1971, 1999.
 279. Hofmann, F., M. Biel, and V. Flockerzi. Molecular basis for Ca2+ channel diversity. Annu. Rev. Neurosci. 17: 399–418, 1994.
 280. Hoffmann, B. F. and P. F. Cranefield. Electrophysiology of the Heart. New York: McGraw‐Hill, 1960.
 281. Hoffman, B. F. and E. E. Suckling. Effect of several cations on transmembrane potentials of cardiac muscle. Am. J. Physiol. 186: 317–324, 1956.
 282. Honore, E., B. Attali, G. Romey, C. Herteaux, P. Ricard, F. Lesage, M. Lazdunski, and J. Barhanin. Cloning, expression, pharmacology and regulation of a delayed rectifier K+ channel in mouse heart. EMBO J. 10: 2805–2811, 1991.
 283. Horie, M., T.‐C. Hwang, and D. C. Gadsby. Pipette GTP is essential for receptor‐mediated regulation of Cl− current in dialysed myocytes from guinea‐pig ventricle. J. Physiol. (Lond.) 455: 235–246, 1992.
 284. Horie, M. and H. Irisawa. Dual effects of intracellular magnesium on muscarinic potassium channel current in single guinea‐pig atrial cells. J. Physiol. (Lond.) 408: 313–332, 1989.
 285. Horie, M., H. Irisawa, and A. Noma. Voltage‐dependent magnesium block of adenosine‐triphosphate‐sensitive potassium channel in guinea‐pig ventricular cells. J. Physiol. (Lond.) 387: 251–272, 1987.
 286. Horowitz, B., S. S. Tsung, P. Hart, P. C. Levesque, and J. R. Hume. Alternative splicing of CFTR Cl‐channels in heart. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H2214–H2220, 1993.
 287. Hosey, M. M., K. K. McMahon, and R. D. Green. Inhibitory adenosine receptors in the heart: characterization by ligand binding studies and effects on beta‐adrenergic receptor stimulated adenylate cyclase and membrane protein phosphorylation. J. Mol. Cell. Cardiol. 16: 931–942, 1984.
 288. Houki, S. Restoration effects of histamine on action potential in potassium‐depolarized guinea‐pig papillary muscle. Arch. Int. Pharmacodyn. Ther. 206: 113–120, 1973.
 289. Hu, K., D. Duan, G. R. Li, and S. Nattel. Protein kinase C activates ATP‐sensitive K+ current in human and rabbit ventricular myocytes. Circ. Res. 78: 492–498, 1996.
 290. Hume, J. R., and R. D. Harvey. Chloride conductance pathways in heart. Am. J. Physiol. 261 (Cell Physiol. 30): C399–C412, 1991.
 291. Hume, J. R. and A. Uehara. Ionic basis of the different action potential configurations of single guinea‐pig atrial and ventricular myocytes. J. Physiol. (Lond.) 368: 525–544, 1985.
 292. Hutter, O. and D. Noble. Anion conductance of cardiac muscle. J. Physiol. (Lond.) 157: 335–350, 1961.
 293. Hutter, O. and W. Trautwein. Vagal and sympathetic effects on the pacemaker fibres in the sinus venosus of the heart. J. Gen. Physiol. 39: 715–733, 1956.
 294. Hwang, T.‐C., M. Horie, A. C. Nairn, and D. C. Gadsby. Role of GTP‐binding proteins in the regulation of mammalian cardiac chloride conductance. J. Gen. Physiol. 99: 465–489, 1992.
 295. Iano, T. L., M. N. Levy, and M. H. Lee. An acceleratory component of the parasympathetic control of heart rate. Am. J. Physiol. 224: 997–1005, 1973.
 296. Iijima, T., H. Irisawa, and M. Kameyama. Membrane currents and their modification by acetylcholine in isolated single atrial cells of the guinea pig. J. Physiol (Lond.) 359: 485–501, 1985.
 297. Ikeda, N., J. Toyama, I. Kodama, and K. Yamada. The role of electrical uncoupling in the genesis of atrioventricular conduction disturbance. J. Mol. Cell. Cardiol. 12: 800–826, 1980.
 298. Imanishi, S. and B. Surawicz. Automatic activity in depolarized guinea pig ventricular myocardium. Characteristics and mechanisms. Circ. Res. 39: 749–7559, 1976.
 299. Imredy, J. P. and D. T. Yue. Mechanism of Ca2+‐sensitive inactivation of L‐type Ca2+ channels. Neuron 12: 1301–1318, 1994.
 300. Inagaki, N., T. Gonoi, J. P. Clement IV, N. Namba, J. Inazawa, G. Gonzales, L. Aguilar‐Bryan, S. Seino, and J. Bryan. Reconstitution of IKATP: An inward rectifier subunit plus the sulfonylurea receptor. Science 270: 1166–1170, 1995.
 301. Inagaki, N., T. Gonoi, J. P. Clement IV, C.‐Z. Zheng, L. Aguilar‐Bryan, J. Bryan, and S. Seino. A family of sulfonylurea receptors determines the pharmacological properties of ATP‐sensitive K+ channels. Neuron 16: 1011–1117, 1996.
 302. Irisawa, H. Comparative physiology of the pacemaker mechanism. Physiol. Rev. 58: 461–498, 1978.
 303. Irisawa, H., H. F. Brown, and W. Giles. Cardiac pacemaking in the sinoatrial node. Physiol. Rev. 73: 197–227, 1993.
 304. Irisawa, H. and R. Sato. Intra‐ and extracellular actions of protons on the calcium current of isolated guinea pig ventricular cells. Circ. Res. 59: 348–355, 1986.
 305. Isenberg, G. Cardiac Purkinje fibres. [Ca2+]i controls steady state potassium conductance. Pflugers Arch. 371: 71–76, 1977.
 306. Isenberg, G. and L. Belardinelli. Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes. Circ. Res. 55: 309–325, 1984.
 307. Isenberg, G. and W. Trautwein. The effect of dihydro‐ouabain and lithium ions on the outward current in cardiac Purkinje fibres. Pflugers Arch. 350: 41–54, 1974.
 308. Ishihara, K., T. Mitsuiye, A. Noma, and M. Takano. The Mg2+ block and intrinsic gating underlying inward rectification of the K+ current in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 419: 297–320, 1989.
 309. Ishikawa, T., M. Yanagisawa, S. Kimura, K. Goto, and T. Masaki. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea‐pig atria. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H970–H973, 1988.
 310. Isomoto, S., C. Kondo, M. Yamada, S. Matsumoto, O. Higashiguchi, Y. Horio, Y. Matsuzawa, and Y. Kurachi. A novel sulfonylurea receptor forms with BIR(Kir6.2) a smooth muscle type ATP‐sensitive K+ channel. J. Biol. Chem. 271: 24321–24324, 1996.
 311. Ito, H., R. T. Tung, T. Sugimoto, I. Kobayashi, K. Takahashi, T. Katada, M. Ui, and Y. Kurachi. On the mechanism of G protein β γ subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. J. Gen. Physiol. 99: 961–983, 1992.
 312. Ito, H., J. Vereecke, and E. Carmeliet. Intracellular protons inhibit inward rectifier K+ channel of guinea pig ventricular cell membrane. Pflugers Arch. 422: 280–286, 1992.
 313. Ito, H., J. Vereecke, and E. Carmeliet. Mode of regulation by G protein of the ATP‐sensitive K+ channel in guinea‐pig ventricular cell membrane. J. Physiol. (Lond). 478: 101–108, 1994.
 314. Iyadomi, I., K. Hirahara, and T. Ehara. α‐Adrenergic inhibition of the β‐adrenoceptor‐dependent chloride current in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 489: 95–104, 1995.
 315. Jahnel, U., H. Nawrath, E. Carmeliet, and J. Vereecke. Depolarization‐induced influx of sodium in response to phenylephrine in rat atrial heart muscle. J. Physiol. (Lond). 432: 621–637, 1991.
 316. James, A. F., L‐H. Xie, Y. Fujitani, S. Hayashi, and M. Horie. Inhibition of the cardiac protein kinase A‐dependent chloride conductance by endothelin‐1. Nature 370: 297–300, 1994.
 317. Janse, M. J. and A. L. Wit. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol. Rev. 69: 1049–1169, 1989.
 318. January, C. and H. A. Fozzard. Delayed afterdepolarizations in heart muscle: mechanism and relevance. Pharmacol. Rev. 40: 219–227, 1988.
 319. Je Zhang, Z., N. K. Jurkiewicz, K. Folander, E. Lazarides, J. J. Salata, and R. Swanson. K+ currents expressed from the guinea pig cardiac Isk protein are enhanced by activators of protein kinase C. Proc. Natl. Acad. Sci. U.S.A. 91: 1766–1779, 1994.
 320. Jo, S.‐H., J. Boum, Y.‐I. Kim, C. O. Lee, Y. E. Earm, and W.‐K. Ho. Blockade of HERG channels expressed in Xenopus oocytes by external H+. Pflugers Arch. 438: 23–29, 1999.
 321. Johnson, E. A. and M. G. McKinnon. Effect of acetylcholine and adenosine on cardiac cellular potentials. Nature 178: 1174–1175, 1956.
 322. Johnson, J. P. Jr., F. M. Mullins, and P. B. Bennett. Human ether‐a‐go‐go‐related gene K+ channel gating probed with extracellular Ca2+. Evidence for two distinct voltage sensors. J. Gen. Physiol. 113: 565–580, 1999.
 323. Josephson, I. R. and N. Sperelakis. Tetrodotoxin differently blocks peak and steady‐state sodium channel currents in early embryonic chick ventricular myocytes. Pflugers Arch. 414: 354–359, 1989.
 324. Jourdon, P. and D. Feuvray. Calcium and potassium currents in ventricular myocytes isolated from diabetes rats. J. Physiol. (Lond.) 470: 411–429, 1993.
 325. Ju, Y. K. and D. G. Allen. Intracellular calcium and Na+‐Ca2+ exchange current in isolated toad pacemaker cells. J. Physiol. (Lond.) 508: 153–166, 1998.
 326. Kaczmarek, L. K., and E. M. Blumenthal. Properties and regulation of the minK potassium channel protein. Physiol. Rev. 77: 627–641, 1997.
 327. Kaibara, M. and M. Kameyama. Inhibition of the calcium channel by intracellular protons in single ventricular myocytes of the guinea‐pig. J. Physiol. (Lond.) 403: 621–640, 1988.
 328. Kaibara, M., T. Nakajima, H. Irisawa, and W. Giles. Regulation of spontaneous opening of muscarinic K+ channels in rabbit atrium. J. Physiol. (Lond.) 433: 589–613, 1991.
 329. Kameyama, M., F. Hofmann and W. Trautwein. On the mechanisms of β‐adrenergic regulation of the Ca channel in the guinea‐pig heart. Pflugers Arch. 405: 285–293, 1985.
 330. Kameyama, M., M. Kakei, R. Sato, T. Shibasaki, H. Matsuda, and H. Irisawa. Intracellular Na+ activates a K+ channel in mammalian cardiac cells. Nature 309: 354–356, 1984.
 331. Kaneda, M., K. Fukui, and K. Doi. Activation of chloride current by P2‐purinoceptors in rat ventricular myocytes. Br. J. Pharmacol. 111: 1355–1360, 1994.
 332. Kantor, P. F., W. A. Coetzee, E. Carmeliet, S. C. Denis, and L. H. Opie. Reduction of ischemic K+ loss and arrhythmias in rat hearts. Effect of glibenclamide, a sulfonylurea. Circ. Res. 66: 478–485, 1990.
 333. Kass, R. S. and M. L. Blair. Effects of angiotensin II on membrane current in cardiac Purkinje fibers. J. Mol. Cell. Cardiol. 13: 797–809, 1981.
 334. Kass, R. S. and M. C. Sanguinetti. Inactivation of calcium channel current in the calf Purkinje fiber. Evidence for voltage‐ and calcium‐mediated mechanisms. J. Gen. Physiol. 84: 705–726, 1984.
 335. Kass, R. S. and R. W. Tsien. Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J. Gen. Physiol. 66: 169–192, 1975.
 336. Kass, R. S. and R. W. Tsien. Control of action potential duration by calcium ions in cardiac Purkinje fibers. J. Gen. Physiol. 67: 599–617, 1976.
 337. Kass, R. S., R. W. Tsien and R. Weingart. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J. Physiol (Lond). 281: 209–226, 1978.
 338. Kassebaum, D. G. Electrophysiological effects of strophanthidin in the heart. J. Pharmacol. Exp. Ther. 140: 329–338, 1963.
 339. Kathofer, S., W. Zhang, C. Karle, D. Thomas, W. Schoels, and J. Kiehn. Functional coupling in human β3‐adrenoceptors to the KvLQT1/ mink potassium channel. J. Biol. Chem. 275: 26743–26747, 2000.
 340. Kato, M., H. Yamaguchi and R. Ochi. Mechanism of adenosine‐induced inhibition of calcium current in guinea pig ventricular cells. Circ. Res. 67: 1134–1141, 1990.
 341. Katzung, B. G. and J. A. Morgenstern. Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium. Circ. Res. 40: 105–111, 1977.
 342. Kaufmann, R. and U. Theophile. Automatie‐fordernde Dehnungseffekte an Purkinje‐faden, Papillarmuskeln and Vorhoftrabekeln von Rhesus‐Affen. Pflugers Arch. 297: 174–189, 1967.
 343. Kaumann, A. J. Four β‐adrenoceptor subtypes in the mammalian heart. Trends Pharmacol Sci. 18: 70–76, 1997.
 344. Kawano, S. and M. Hiraoka. Transient outward currents and action potential alterations in rabbit ventricular myocytes. J. Mol. Cell. Cardiol. 23: 681–693, 1991.
 345. Kawano, S., Y. Hirayama and M. Hiraoka. Activation mechanism of Ca2+‐sensitive transient outward current in rabbit ventricular myocytes. J. Physiol. (Lond.) 486: 593–604, 1995.
 346. Kelly, R. A., J.‐L. Balligand, and T. W. Smith. Nitric oxide and cardiac function. Circ. Res. 79: 363–380, 1996.
 347. Kim, D. Endothelin activation of an inwardly rectifying K+ current in atrial cells. Circ. Res. 69: 250–255, 1991.
 348. Kim, D. A mechanosensitive K+ channel in heart cells: activation by arachidonic acid. J. Gen. Physiol. 100: 1021–1040, 1992.
 349. Kim, D., T. W. Smith, and J. D. Marsh. Effect of thyroid hormone on slow calcium channel function in cultured chick ventricular cells. J. Clin. Invest. 80: 88–94, 1987.
 350. Kimura, S., J. S. Cameron, P. L. Kozlovskis, A. L. Basset, and R. J. Myerberg. Delayed afterdepolarization and triggered activity induced in feline Purkinje fibers by α‐adrenergic stimulation in the presence of elevated calcium level. Circulation 70: 1074–1082, 1984.
 351. Kimura, J., S. Miyamae, and A. Noma. Identification of sodium‐calcium exchange current in single ventricular cells of guinea‐pig. J. Physiol. (Lond). 384: 199–222, 1987.
 352. Kingsley, P. B., E. Y. Sako, M. Q. Yang, S. D. Zimmer, K. Ugurbi, J. E. Foker, and A. H. L. From. Ischemic contracture begins when anaerobic glycolysis stops: a 31P‐NMR study of isolated rat hearts. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H469–H478, 1991.
 353. Kirsch, G. E., J. Codina, L. Birnbaumer, and A. M. Brown. Coupling of ATP‐sensitive K+ channels to A1 receptors by G protein in rat ventricular myocytes. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H820–H826, 1990.
 354. Kirsch, G. E. and J. S. Sykes. Temperature dependence of Na currents in rabbit and frog muscle membrane. J. Gen. Physiol. 89: 239–251, 1987.
 355. Kishida, H., B. Surawicz, and L. T. Fu. Effects of K+ and K+‐induced polarization on (dV/dt)max threshold potential, and membrane input resistance in guinea pig and cat ventricular myocardium. Circ. Res. 44: 800–814, 1979.
 356. Kiyosue, T. and M. Arita. Late sodium current and its contribution to action potential configulation in guinea pig ventricular myocytes. Circ. Res. 64: 389–397, 1989.
 357. Kiyosue, T., M. Arita, H. Muramatsu, A. J. Spindler, and D. Noble. Ionic mechanisms of action potential prolongation at low temperature in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 468: 85–106, 1993.
 358. Kiyosue, T., A. J. Spindler, S. J. Noble, and D. Noble. Background inward current in ventricular and atrial cells of the guinea‐pig. Proc. R. Soc. Lond. B. Biol. Sci. 252: 65–74, 1993.
 359. Kobayashi, S., H. Nakaya, T. Takizawa, S. Hara, S. Kimura, T. Saito, and Y. Masuda. Endothelin‐1 partially inhibits ATP‐sensitive K+ current in guinea pig ventricular cells. J. Cardiovasc. Pharmacol. 27: 12–19, 1996.
 360. Kohlhardt, M. and K. Happ. 8‐Bromo‐guanosine‐3′, 5′‐monophosphate mimics the effect of acetylcholine on slow response action potential and contractile force in mammalian atrial myocardium. J. Mol. Cell. Cardiol. 19: 573–586, 1978.
 361. Kohlhardt, M., H. P. Haastert, and H. Krause. Evidence of nonspecificity of the Ca channel in mammalian myocardial fibre membranes. Substitution of Ca by Sr, Ba or Mg as charge carriers. Pflugers Arch. 342: 125–136, 1973.
 362. Kojima, M., H. Sada, and N. Sperelakis. Developmental changes in β‐adrenergic and cholinergic interactions on calcium‐dependent slow action potentials in rat ventricular muscles. Br. J. Pharnacol. 99: 327–333, 1990.
 363. Korth, M. and V. Kuhlkamp. Muscarinic receptor‐mediated increase of intracellular Na+‐ion activity and force of contraction. Pflugers Arch. 403: 266–272, 1985.
 364. Krafte, D. E. and R. S. Kass. Hydrogen ion modulation of Ca channel current in cardiac ventricular cells. Evidence for multiple mechanisms. J. Gen. Physiol. 91: 641–657, 1988.
 365. Krapivinsky, G., E. A. Gordon, K. Wickman, B. Vellmirovic, L. Krapivinsky and D. E. Clapham. The G‐protein‐gated atrial K+‐channel IK.ACh is a heteromultimer of two inwardly rectifying K+‐channel proteins. Nature 374: 135–141, 1995.
 366. Kukushkin, N. I., R. Z. Guinullin, and E. A. Sosunov. Transient outward current and rate dependence of action potential duration in rabbit cardiac ventricular muscle. Pflugers Arch. 399: 87–92, 1983.
 367. Kunapuli, S. P. and J. L. Daniel. P2 receptor subtypes in the cardiovascular system. Biochem J. 336: 513–523, 1998.
 368. Kunze, D. Rate dependent changes in extracellular potassium in rabbit atrium. Circ. Res. 41: 122–127, 1977.
 369. Kunze, D. L., A. E. Lacerda, D. L. Wilson, and A. M. Brown. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J. Gen. Physiol. 86: 691–719, 1985.
 370. Kuo, J. F., T. P. Lee, P. L. Reyes, K. G. Walton, T. E. Donnelly, and P. Greengard. Cyclic nucleotide‐dependent protein kinases. X. An assay method for the measurement of guanosin 3′, 5′ monophosphate in various biological materials and a study of agents regulating its level in heart and brain. J. Biol. Chem. 247: 16–22, 1972.
 371. Kurachi, Y. The effects of intracellular protons on the electrical activity of single ventricular cells. Pflugers Arch. 394: 264–270, 1982.
 372. Kurachi, Y. Voltage‐dependent activation of the inward‐rectifier potassium channel in the ventricular cell membrane of guineapig heart. J. Physiol. (Lond.) 366: 365–385, 1985.
 373. Kurachi, Y., H. Ito, T. Sugimoto, T. Shimizu, I. Miki, and M. Ui. α‐Adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites. Pflugers Arch. 414: 102–104, 1989.
 374. Kurachi, Y., T. Nakajima, and T. Sugimoto. On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: involvement of GTP‐binding proteins. Pflugers Arch. 407: 264–274, 1986.
 375. Kurachi, Y., T. Nakajima, and T. Sugimoto. Role of intracellular Mg2+ in the activation of muscarinic K+ channel in cardiac atrial cell membrane. Pflugers Arch. 407: 572–574, 1986.
 376. Kurachi, Y., T. Nakajima, and T. Sugimoto. Short‐term desensitization of muscarinic K+ channel current in isolated atrial myocytes and possible role of GTP‐binding proteins. Pflugers Arch. 410: 227–233, 1987.
 377. Kurtz, T., K. A. Yamada, S. D. DaTorre, and P. B. Corr. Alpha1‐adrenergic system and arrhythmias in ischemic heart disease. Eur. Heart J. 12 (Suppl. F): 88–98, 1991.
 378. Kuruma, A., M. Hiraoka, and S. Kawano. Activation of Ca2+‐sensitive Cl‐ current by reverse mode Na+/Ca2+ exchange in rabbit ventricular myocytes. Pflugers Arch. 436: 976–983, 1998.
 379. Kwatra, M. M., E. Leung, A. C. Maan, K. K. McMahon, J. Ptasienski, R. D. Green and M. M. Hosey. Correlation of agonist‐induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J. Biol. Chem. 262: 16314–16321, 1987.
 380. Kwok, W. M. and R. S. Kass. Block of cardiac ATP‐sensitive K+ channels by external divalent cations is modulated by intracellular ATP. Evidence for allosteric regulation of the channel protein. J. Gen. Physiol. 102: 693–712, 1993.
 381. Lab, M. J. Transient depolarization and action potential alterations following mechanical changes in isolated myocardium. Cardiovasc. Res. 14: 624–637, 1980.
 382. Lab, M. J. Mechanoelectrical feedback (transduction) in heart: concepts and implication. Cardiovasc. Res. 32: 3–14, 1996.
 383. LaManna, V. R. and G. F. Ferrier. Electrophysiological effects of insulin on normal and depressed cardiac tissue. Am. J. Physiol. 240 (Heart Circ. Physiol. 9): H636–H644, 1981.
 384. Lang, F., G. L. Busch, M. Rotter, H. Volkl, S. Waldegger, E. Gulbins, and D. Haussinger. Functional significance of cell volume regulatory mechanisms. Physiol. Rev. 78: 247–306, 1998.
 385. Lansman, J. B., P. Hess, and R. W. Tsien. Blockade of current through single calcium channels by Cd2+, Mg2+. Voltage and concentration dependence of calcium entry into the pore. J. Gen. Physiol. 88: 321–347, 1986.
 386. Lantz, R. C., L. J. Elsas, and R. L. DeHaan. Ouabain‐resistant hyperpolarization induced by insulin in aggregates of embryonic heart cells. Proc. Natl. Acad. Sci. U.S.A. 77: 3062–3066, 1980.
 387. Lauer, M. R., M. D. Gunn, and W. T. Clusin. Endothelin activates voltage‐dependent Ca2+ current by a G protein‐dependent mechanism in rabbit cardiac myocytes. J. Physiol. (Lond.) 448: 729–747, 1992.
 388. Lauer, M. R., B. F. Rusy, and L. D. Davis. H+‐induced membrane depolarization in canine cardiac Purkinje fibers. Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H312–H321, 1984.
 389. Leach, R. N., K. Brickley, and R. I. Norman. Cyclic AMP‐dependent protein kinase phosphorylates residues in the C‐terminal domain of the cardiac L‐type calcium channel alpha subunit. Biochim. Biophys. Acta 1281: 205–212, 1996.
 390. Lederer, W. J. and C. G. Nichols. Nucleotide modulation of the activity of the rat heart ATP‐sensitive K+ channels in isolated membrane patches. J. Physiol. (Lond.) 419: 193–211, 1989.
 391. Lederer, W. J. and R. W. Tsien. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J. Physiol (Lond). 263: 73–100, 1976.
 392. Lee, C. O. 200 years of digitalis: the emerging central role of the sodium ion in the control of cardiac force. Am. J. Physiol. 249 (Cell Physiol. 18): C367–C378, 1985.
 393. Lee, C. O. and H. A. Fozzard. Activities of potassium and sodium in rabbit heart muscle. J. Gen. Physiol. 65: 694–708, 1975.
 394. Lee, C. O. and A.J. Levi. The role of intracellular sodium in the control of cardiac contraction. Ann. N.Y. Acad, Sci. 639: 408–428, 1991.
 395. Lee, J. H. and M. R. Rosen. Modulation of delayed afterdepolarizations by α 1‐adrenergic receptor subtypes. Cardiovasc. Res. 27: 839–844, 1993.
 396. Lee, K. S. Potentiation of the calcium‐channel currents of internally perfused mammalian heart cells by repetitive depolarization. Proc. Natl. Acad. Sci. U.S.A. 405: 3941–3945, 1987.
 397. Lee, K. S. and W. Klaus. The subcellular basis for the mechanism of inotropic action of cardiac glycosides. Pharmacol. Rev. 23: 193–261, 1971.
 398. Lee, K. S., E. Marban, and R. W. Tsien. Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium. J. Physiol. (Lond.). 364: 395–411, 1985.
 399. Legaye, F., P. Biegelman, E. Doroubaix, and E. Coraboeuf. Effect of 3–5–3′triiodothyronine treatment on cardiac action potential of streptozotocin‐induced diabetic rat. Life Sci. 42: 2269–2274, 1988.
 400. Le Grand, B., E. Deroubaix, J.‐P. Couetil, and E. Coraboeuf. Effects of atrionatriuretic factor on Ca2+ current and Cai‐independent transient outward K+ current in human atrial cells. Pflugers Arch. 421: 486–491, 1992.
 401. Le Grand, B., E. Deroubaix, A. Coulombe, and E. Coraboeuf. Stimulatory effect of ouabain on T‐ and L‐type calcium currents in guinea‐pig cardiac myocytes. Am. J. Physiol. 258 (Heart Circ. Physiol. 27) H1620–H1623, 1990.
 402. Le Guennec, J.‐V. and D. Noble. Effects of rapid changes of external Na+ concentration at different moments during the action potential in guinea‐pig myocytes. J. Physiol. (Lond.) 478: 493–504, 1994.
 403. Levi, A. J. The effect of strophanthidin on action potential, calcium current and contraction in isolated guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 443: 1–23, 1991.
 404. Levi, A. J. A role for Na/Ca exchange in the action potential shortening caused by strophanthidin in guinea‐pig ventricular myocytes. Cardiovasc. Res. 27: 471–481, 1993.
 405. Levi, A. J., M. R. Boyett, and C. O. Lee. The cellular actions of digitalis glycosides on the heart. Prog. Biophys. Mol. Biol. 62: 1–54, 1994.
 406. Levi, R. C. and G. Alloatti. Histamine modulates calcium current in guinea pig ventricular myocytes. J. Pharmacol. Exp. Ther. 246: 337–343, 1988.
 407. Levi, R. C., G. Alloatti, and R. Fischmeister. Cyclic GMP regulates the Ca‐channel current in guinea pig ventricular myocytes. Pflugers Arch. 413: 685–687, 1989.
 408. Levi, R. C., G. Alloatti, C. Penna, and M. P. Gallo. Guanylatecyclase‐mediated inhibition of cardiac ICa by carbachol and sodium nitroprusside. Pflugers Arch. 426: 419–426, 1994.
 409. Levi, R. C., D. A. A. Owen, and J. Trzeciakowski. Actions of histamine on the heart and vasculature. In Pharmacology of Histamine Receptors, edited by R. Ganellin and M. Parsons. London: J Wright, 1982: 236–297.
 410. Levi, R. C. and A. J. Pappano. Modification of the effects of histamine and norepinephrine on the sinoatrial node pacemaker by potassium and calcium. J. Pharmacol. Exp. Ther. 204: 625–633, 1978.
 411. Li, G. R., J. Feng, A. Schrier, and S. Nattel. Contribution of the ATP‐sensitive potassium channels to the electrophysiological effects of adenosine in guinea‐pig atrial cells. J. Physiol. (Lond). 484: 629–642, 1995.
 412. Li, Y., R. Hanf, A. S. Otero, R. Fischmeister, and G. Szabo. Differential effects of pertussis toxin on the muscarinic regulation of Ca2+ and K+ currents in frog cardiac myocytes. J. Gen. Physiol. 104: 941–959, 1994.
 413. Li, Y. and R. A. Kloner. The cardioprotective effects of ischemic “preconditioning” are not mediated by adenosine receptors in rat heart. Circulation 87: 1642–1648, 1993.
 414. Light, P. Regulation of ATP‐sensitive potassium channels by protein phosphorylation. Biochim. Biophys. Acta 1286: 65–73, 1996.
 415. Light, P. E., B. G. Allen, M. P. Walsh, and R. J. French. Regulation of adenosine triphosphate‐sensitive potassium channels from rabbit ventricular myocytes by protein kinase C and type 2A protein phosphatase. Biochemistry 34: 7252–7257, 1995.
 416. Lin, Y‐F., Y. N. Jan, and L. Y. Jan. Regulation of ATP‐sensitive potassium channel function by protein kinase A–mediated phosphorylation in transfected HEK293 cells. EMBO J. 19: 942–955, 2000.
 417. Lindemann, J. P. and A. M. Watanabe. Muscarinic cholinergic inhibition of β‐adrenergic stimulation of phospholamban phosphorylation and Ca2+ transport in guinea pig ventricles. J. Biol. Chem. 260: 13122–13129, 1985.
 418. Lipp, P., S. Mechmann, and L. Pott. Effects of calcium release from sarcoplasmic reticulum on membrane currents in guinea pig atrial cardioballs. Pflugers Arch. 410: 121–131, 1987.
 419. Lipsius, S. L. and W. R. Gibbons. Acetylcholine lengthens action potentials of sheep cardiac Purkinje fibers. Am. J. Physiol. 238 (Heart Circ. Physiol. 7): H237–H243, 1980.
 420. Liu, G. S., J. D. Thornton, D. M. Van Winkel, A. W. H. Stanley, R. A. Olsson, and J. M. Downey. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 84: 350–356, 1991.
 421. Liu, Q‐Y., E. Karpinski, and P. K. Pang. The L‐type calcium channel current is increased by alpha‐1 adrenoceptor activation in neonatal rat ventricular cells. J. Pharmacol. Exp. Ther. 271: 935–943, 1994.
 422. Liu, S. J. and R. H. Kennedy. α1‐Adrenergic activation of L‐type Ca current in rat ventricular myocytes: perforated patchclamp recordings. Am. J. Physiol. 274 (Heart Circ. Physiol. 41): H2203–H2207, 1998.
 423. Liu, Y., T. Sato, B. O'Rourke, and E. Marban. Mitochondrial ATP‐dependent potassium channels: novel effectors of cardioprotection? Circulation 97: 2463–2469, 1998.
 424. Lo, C. F., and R. Numann. Independent and exclusive modulation of cardiac delayed rectifying K+ current by protein kinase C and protein kinase A. Circ. Res. 83: 995–1002, 1998.
 425. Logothetis, D. E., Y. Kurachi, J. Galper, E. J. Neer, and D. E. Clapham. The β γ subunits of GTP‐binding proteins activate the muscarinic K+ channels in heart. Nature 325: 321–326, 1987.
 426. Lu, Z. and R. MacKinnon. Electrostatic tuning of Mg2+ affinity in an inward rectifier K+ channel. Nature 371: 243–246, 1994.
 427. Luk, H. N. and E. Carmeliet. Na+‐activated K+ current in cardiac cells: rectification, open probability, block, and role in digitalis toxicity. Pflugers Arch. 416: 766–768, 1990.
 428. MacDonnel, K. L., G. F. Tibbits, and L. Diamond. cGMP elevation does not mediate muscarinic agonist‐induced negative inotropy in rat ventricular cardiomyocytes. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1905–H1912, 1995.
 429. Magyar, J., Z. Rusznak, P. Szentesi, G. Szucs, and L. Kovacs. Action potentials and potassium currents in rat ventricular muscle during experimental diabetes. J. Mol. Cell. Cardiol. 24: 841–853, 1992.
 430. Marban, E. and R. W. Tsien. Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feedback regulation by intracellulr calcium? J. Physiol. (Lond.) 329: 589–614, 1982.
 431. Marban, E., T. Yamagishi, and G. T. Tomaselli. Structure and function of voltage‐gated sodium channels. J. Physiol. (Lond.) 508: 647–657, 1998.
 432. Martin, P., M. N. Levy, and Y. Matsuda. Fade of cardiac responses during tonic vagal stimulation. Am. J. Physiol. 243 (Heart Circ. Physiol. 12): H219–H225, 1982.
 433. Masaki, T., M. Yanagisawa, and K. Goto. Physiology and pharmacology of endothelins. Med. Res. Rev. 12: 391–421, 1992.
 434. Masuda, H. and N. Sperelakis. Inwardly rectifying potassium current in rat fetal and neonatal ventricular cardiomyocytes. Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H1107–H1111, 1993.
 435. Matsuda, H. Sodium conductance in calcium channels of guinea‐pig ventricular cells induced by removal of external calcium ions. Pflugers Arch. 407: 465–475, 1986.
 436. Matsuda, H. and J. D. S. Cruz. Voltage‐dependent block by internal Ca2+ ions of inwardly rectifying K+ channels in guineapig ventricular cells. J. Physiol (Lond). 470: 295–311, 1993.
 437. Matsuda, H., A. Saigusa, and H. Irisawa. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature 325: 156–159, 1987.
 438. Matsuda, J. J., H. Lee, and E. F. Shibata. Enhancement of rabbit cardiac sodium channels by β‐adrenergic stimulation. Circ. Res. 70: 199–207, 1992.
 439. Matsuda, J. J., H. Lee and E. F. Shibata. Acetylcholine reversal of isoproterenol‐stimulated sodium currents in rabbit ventricular myocytes. Circ. Res. 72: 517–525, 1993.
 440. Matsumoto, K. and A. J. Pappano. Sodium‐dependent membrane current induced by carbachol in single guineapig ventricular myocytes. J. Physiol. (Lond.) 415: 487–502, 1989.
 441. Matsuura, H. and T. Ehara. Activation of chloride current by purinergic stimulation in guinea pig heart cells. Circ. Res. 70: 851–855, 1992.
 442. Matsuura, H., and T. Ehara. Modulation of the muscarinic K+ channel by P2‐purinoceptors in guinea‐pig atrial myocytes. J. Physiol. (Lond.) 497: 379–393, 1996.
 443. Matsuura, H., M. Sakaguchi, Y. Tsuruhara, and T. Ehara. Activation of the muscarinic K+ channel by P2‐purinoceptors via pertussis toxin‐sensitive G protein in guinea‐pig atrial cells. J. Physiol. (Lond.) 490: 659–671, 1996.
 444. Matsuura, H., Y. Tsuruhara, M. Sakaguchi, and T. Ehara. Enhancement of delayed rectifier K+ current by P2‐purinoceptor stimulation in guinea‐pig atrial cells. J. Physiol. (Lond.) 490: 647–658, 1996.
 445. McDonald, T. F., S. Pelzer, W. Trautwein, and D. J. Pelzer. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol. Rev. 74: 365–507, 1994.
 446. McDonald, T. F. and W. Trautwein. The potassium current underlying delayed rectification in cat ventricular muscle. J. Physiol. (Lond.) 274: 217–246, 1978.
 447. Meijler, F. L. and M. J. Janse. Morphology and electrophysiology of the mammalian atrioventricular node. Physiol. Rev. 68: 608–647, 1988.
 448. Mentrand, D., G. Vassort, and R. Fischmeister. Calciummediated inactivation of the calcium conductance in cesiumloaded frog heart cells. J. Gen. Physiol. 83: 105–131, 1984.
 449. Mery, P.‐F., N. Abi‐Gerges, G. Vandecasteele, J. Jurevicius, T. Eschenhagen, and R. Fischmeister. Muscarinic regulation of the L‐type calcium current in isolated cardiac myocytes. Life Sci. 60: 1113–1120, 1997.
 450. Mery, P.‐F., L. Hove‐Madsen, J.‐M. Chesnais, H. C. Hartzell, and R. Fischmeister. Nitric oxyde synthase does not participate in negative inotropic effect of acetylcholine in frog heart. Am. J. Physiol. 270 (Heart Circ. Physiol. 39): H1178–H1188, 1996.
 451. Mery, P.‐F., S. M. Lohmann, U. Walter, and R. Fischmeister. Ca2+ current is regulated by cyclic GMP‐dependent protein kinase in mammalian cardiac myocytes. Proc. Natl. Acad. Sci. U.S.A. 88: 1197–1201, 1991.
 452. Michel, M. C., B. Kenny, and D. A. Schwinn. Classification of α1‐adrenoceptor subtypes. N‐S. Arch. Pharmacol. 352: 1–10, 1995.
 453. Mills, J. W., E. M. Schwiebert, and B. A. Stanton. The cytoskeleton and cell volume regulation. In: Cellular and Molecular Physiology of Cell Volume Regulation, edited by K. Strange. Ann Arbor, MI: CRC, 1994: 241–258.
 454. Minneman, K. P. α1‐Adrenergic receptor subtypes, inositol phosphates, and sources of cell Ca2+. Pharmacol. Rev. 40: 87–119, 1988.
 455. Mitchell, M. R., T. Powell, D. A. Terrar, and V. W. Twist. Calcium‐activated inward current and contraction in rat and guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 391: 545–560, 1987.
 456. Miura, Y. and J. Inui. Multiple effects of α‐adrenoceptor stimulation on the action potential of the rabbit atrium. N‐S. Arch. Pharmacol. 325: 47–53, 1984.
 457. Molenaar, P., G. O'Reilly, A. Sharkey, R. E. Kuc, D. P. Harding, C. Plumpton, G. A. Gresham, and A. P. Davenport. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ. Res. 72: 526–538, 1993.
 458. Moore, R. D. Effects of insulin upon ion transport. Biochim. Biophys. Acta 737: 1–49, 1983.
 459. Moorman, J. R., G. E. Kirsch, A. E. Lacerda, and A. M. Brown. Angiotensin II modulates cardiac Na+ channels in neonatal rat. Circ. Res. 65: 1804–1809, 1989.
 460. Morita, H., J. Kimura, and M. Endoh. Angiotensin II activation of a chloride current in rabbit cardiac myocytes. J. Physiol. (Lond.) 483; 119–130, 1995.
 461. Morkin, E., I. L. Flink, and S. Goldman. Biochemical and physiological effects of thyroid hormone on cardiac performance. Prog. Cardiovasc. Dis. 25: 435–465, 1983.
 462. Mubagwa, K. and E. Carmeliet. Effects of acetylcholine on electrophysiological properties of rabbit cardiac Purkinje fibers. Circ. Res. 53: 740–751, 1983.
 463. Mubagwa, K., T. Shirayama, M. Moreau, and A. J. Pappano. Effects of PDE inhibitors and carbachol on the L‐type Ca current in guinea pig ventricular myocytes. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H1353–H1363, 1993.
 464. Mugelli, A., L. Mantelli, S. Manzini, and F. Ledda. Induction by histamine of oscillatory activity in sheep Purkinje fibers and suppression by verapamil and lidocaine. J. Cardiovasc. Pharmacol. 2: 9–15, 1980.
 465. Murphy, B. J., J. Roger, A. P. Pedichizzi, A. A. Calvin, and W. A. Catterall. . cAMP‐dependent phosphorylation of two sites in the alpha subunit of the cardiac sodium channel. J. Biol. Chem. 271: 28837–28843, 1996.
 466. Murray, K. T., S. A. Fahrig, K. K. Deal, S. S. Po, N. N. Hu, D. J. Snyder, M. M. Tamkun, and P. B. Bennett. Modulation of an inactivating human cardiac K+ channel by protein kinase C. Circ. Res. 75: 999–1005, 1994.
 467. Murray, K. T., N. N. Hu, J. R. Daw, H‐G. Shin, M. T. Watson, A. B. Mashburn, and A. L. George, Jr. Functional effects of protein kinase C activation on the human cardiac Na+ channel. Circ. Res. 80: 370–376, 1997.
 468. Murry, C. E., R. B. Jennings, and K. A. Reimer. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74: 1124–1136, 1986.
 469. Musialek, P., M. Lei, H. F. Brown, D. J. Paterson, and B. Casadei. Nitric oxide can increase heart rate by stimulating the hyperpolarization‐activated inward current, I(f). Circ. Res. 81: 60–68, 1997.
 470. Nakajima, T., S. Wu, H. Irisawa, and W. Giles. Mechanism of acetylcholine‐induced inhibition of Ca current in bullfrog atrial myocytes. J. Gen. Physiol. 96: 865–885, 1990.
 471. Nakamura, S., T. Kiyosue, and M. Arita. Glucose reserves, 2, 4‐dinitrophenol induced changes in action potentials and membrane currents of guinea pig ventricular cells via enhanced glycolysis. Cardiovasc. Res. 23: 286–294, 1989.
 472. Nakayama, K., Z. Fan, F. Marumo, and M. Hiraoka. Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP‐sensitive K+ current in guinea‐pig ventricular myocytes. Circ. Res. 67: 1124–1133, 1990.
 473. Nakayama, K., Z. Fan, F. Marumo, T. Sawanobori, and M. Hiraoka. Action of nicorandil on ATP‐sensitive K+ channel in guinea‐pig ventricular myocytes. Br. J. Pharmacol. 103: 1461–1468, 1991.
 474. Nakayama, T., Y. Kurachi, A. Noma, and H. Irisawa. Action potential and membrane currents of single pacemaker cells of the rabbit heart. Pflugers Arch. 402: 248–57, 1984.
 475. Nattel, S., V. Elharrar, D. P. Zilpes, and J. C. Bailey. pH dependent electrophysiological effects of quinidine and lidocaine on canine cardiac Purkinje fibers. Circ. Res. 48: 55–61, 1981.
 476. Neyses, L., and H. Vetter. Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes. Biochem. Biophys. Res. Commun. 163: 1435–1443, 1989.
 477. Nichols, C. G. and W. J. Lederer. Adenosine triphosphatesensitive potassium channels in the cardiovascular system. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1675–H1686, 1991.
 478. Niedergerke, R. and R. K. Orkand. The dependence of the action potential of the frog's heart on the external and intracellular sodium concentration. J. Physiol. (Lond.) 184: 312–334, 1966.
 479. Nilius, B. Calcium block of guinea‐pig heart sodium channels with and without modification by the piperazinylindolem DPI 201–106. J. Physiol. (Lond.) 399: 537–558, 1988.
 480. Nilius, B., J. Tytgart, and R. Albitz. Modulation of cardiac Na channels by angiotensin II. Biochim. Biophys. Acta 1014: 259–262, 1989.
 481. Nishiyama, A., F. Kambe, K. Kamiya, H. Seo, and J. Toyama. Effects of thyroid status on expression of voltage‐gated potassium channels in rat ventricle. Cardiovasc. Res. 40: 343–351, 1998.
 482. Nitta, J., T. Furukawa, F. Marumo, T. Sawanobori, and M. Hiraoka. Subcellular mechanism of Ca2+‐dependent enhancement of Ik in isolated membrane patches of guinea‐pig ventricular myocytes. Circ. Res. 74: 96–104, 1994.
 483. Noble, D. Electrical properties of cardiac muscle attributable to inward‐going (anomalous) rectification. J. Cell. Comp. Physiol. 66: 127–136, 1965.
 484. Noma, A., H. Irisawa, S. Kokubun, H. Kotake, M. Nishimura, and Y. Watanabe. Slow current system in the A‐V node of the rabbit heart. Nature 285: 228–229, 1980.
 485. Noma, A., H. Kotake, and H. Irisawa. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node. Pflugers Arch. 388: 1–9, 1980.
 486. Noma, A., T. Nakayama, Y. Kurachi, and H. Irisawa. Resting K conductance in pacemaker and non‐pacemaker heart cells of the rabbit. Jpn. J. Physiol. 34: 245–254, 1984.
 487. Noma, A. and W. Trautwein. Relaxation of the ACh‐induced potassium current in the rabbit sino‐atrial node. Pflugers Arch. 377: 193–200, 1978.
 488. Noma, A. and N. Tsuboi. Dependence of junctional conductance on proton, calcium and magnesium ions in cardiac paired cells of guinea pig. J. Physiol. (Lond.) 382: 193–211, 1987.
 489. Notsu, T., I. Tanaka, M. Takano, and A. Noma. Blockade of the ATP‐sensitive K+ channel by 5‐hydroxydecanoate in guinea pig ventricular myocytes. J. Pharmacol. Exp. Ther. 260: 702–708, 1992.
 490. Nunain, S. O., C. Garrat, V. Paul, N. Debbas, D. E. Ward, and A. J. Camm. Effect of intravenous adenosine on human atrial and ventricular repolarisation. Cardiovasc. Res. 26: 939–943, 1992.
 491. Nuss, H. B., E. Marban, C. W. Balke, L. Goldman, R. Aggarwal, and S. R. Shrofsky. Whether “slip‐mode conductance” occurs. Science 284: 711a, 1999.
 492. Obayashi, K., M. Horie, L. H. Xie, K. Tsuchiya, A. Kubota, H. Ishida, and S. Sasayama. Angiotensin II inhibits protein kinase A‐dependent chloride conductance in heart via pertussis toxinsensitive G proteins. Circulation 95: 197–204, 1997.
 493. Ochi, R. Manganese‐dependent propagation potentials and their depression by electrical stimulation in guinea‐pig myocardium perfused by sodium‐free media. J. Physiol. (Lond). 263: 139–156, 1976.
 494. Ochi, R. and Y. Kawashima. Modulation of slow gating process of calcium channels by isoprenaline in guinea‐pig ventricular cells. J. Physiol (Lond.) 424: 184–204, 1990.
 495. Ohno‐Shosaku, T., B. J. Zunkler, and G. Trube. Dual effects of ATP and K+ currents of mouse pancreatic β‐cells. Pflugers Arch. 410: 133–138, 1987.
 496. Oleska, L. M., L. C. Hool, and R. D. Harvey. α1‐Adrenergic inhibition of the β‐adrenergically activated Cl− current in guinea pig ventricular myocytes. Circ. Res. 78: 1090–1099, 1996.
 497. Olsson, R. A. and J. D. Pearson. Cardiovascular purinoreceptors. Physiol. Rev. 70: 761–845, 1990.
 498. Ono, K., G. Tsujimoto, A. Sakamoto, K. Eto, T. Masaki, Y. Ozeki, and M. Satake. Endothelin‐A receptor mediates cardiac inhibition by regulating calcium and potassium currents. Nature 370: 301–304, 1994.
 499. Ono, K. and H. A. Fozzard. Two phosphatase sites on the Ca2+ channel affecting different kinetic functions. J. Physiol. (Lond). 470: 73–84, 1993.
 500. Ono, K., H. A. Fozzard, and D. A. Hanck. Mechanism of cAMP‐dependent modulation of cardiac sodium channel current kinetics. Circ. Res. 72: 807–815, 1993.
 501. Ono, K. and H. Ito. Role of rapidly activating delayed rectifier K+ current in sinoatrial node pacemaker activity. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H453–H462, 1995.
 502. Ono, K., T. Kiyosue, and M. Arita. Isoproterenol, DBcAMP, and forskolin inhibit cardiac sodium current. Am. J. Physiol. 256 (Cell Physiol. 25): C1131–C1137, 1989.
 503. Ono, K., F. Maruoka, and A. Noma. Voltage‐and timedependent block of If by Sr2+ in rabbit sino‐atrial node cells. Pflugers Arch. 427: 437–443, 1994.
 504. Ono, K., F. M. Tareen, A. Yoshida, and A. Noma. Synergistic action of cyclic GMP on catecholamine‐induced chloride current in guinea‐pig ventricular cells. J. Physiol. (Lond.) 453: 647–661, 1992.
 505. Ono, K. and W. Trautwein. Potentiation by cyclic GMP of β‐adrenergic effect on Ca2+ current in guinea‐pig ventricular cells. J. Physiol. (Lond.) 443: 387–404, 1991.
 506. Orchard, C. H. and H. E. Cingolani. Acidosis and arrhythmias in cardiac muscle. Cardiovasc. Res. 28: 1312–1319, 1994.
 507. Orchard, C. H., S. R. Houser, A. A. Kort, A. A. Bahinski, M. C. Capogrossi, and E. G. Lakatta. Acidosis facilitates spontaneous sarcoplasmic Ca2+ release in rat myocardium. J. Gen. Physiol. 90: 145–165, 1987.
 508. O'Rourke, B., P. H. Backx, and E. Marban. Phosphorylationindependent modulation of L‐type calcium channels by magnesium‐nucleotide complexes. Science 257: 245–248, 1992.
 509. Osterrieder, W., Q. F. Yang, and W. Trautwein. Effects of barium ions on the membrane currents in the rabbit S‐A node. Pflugers Arch. 394: 78–84, 1982.
 510. Otero, A. S., G. E. Breitwieser, and G. Sabo. Activation of muscarinic potassium currents by ATP‐γ S in atrial cells. Science 242: 443–445, 1988.
 511. Oz, M. C. and S. Sorota. Forskolin stimulates swelling‐induced chloride current, not cardiac cystic fibrosis transmembrane‐conductance regulator current in human cardiac myocytes. Circ. Res. 76: 1063–1070, 1995.
 512. Pachucki, J., L. A. Burmeister, and P. R. Larsen. Thyroid hormone regulates hyperpolarization‐activated cyclic nucleotidegated channel (HCN2) mRNA in the rat heart Circ. Res. 85: 498–503, 1999.
 513. Pappano, A. J. Parasympathetic control of cardiac electrical activity. In: Cardiac Electrophysiology: From Cell to Bedside. edited by D. P. Zipes, and J. Jalife. Philadelphia: W. B. Saunders 1990: 271–277.
 514. Pappano, A. J. Vagal stimulation of the heart beat: muscarinic receptor hypothesis. J. Cardiovasc. Electrophysiol. 2: 262–273, 1991.
 515. Pappano, A. J. and N. Sperelakis. Low K conductance and low resting potentials of isolated single cultured heart cells. Am. J. Physiol. 217: 1076–1082, 1969.
 516. Parker, K. E. and A. Scarpa. An ATP‐activated nonselective cation channel in guinea pig ventricular myocytes. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H789–H797, 1995.
 517. Patlak, J. B. and M. Oritz. Slow currents through single sodium channels of the adult rat heart. J. Gen. Physiol. 86: 89–104, 1985.
 518. Perets, T., Y. Blumenstein, E. Shistik, I. Lotan, and N. Dascal. A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel alpha 1C subunit. FEBS Lett. 384: 189–192, 1996.
 519. Perez‐Reyes, E., W. Yang, X. Wei, and D. M. Bers. Regulation of the cloned L‐type cardiac calcium channel by cyclic‐AMP‐dependent protein kinase. FEBS Lett. 342: 119–123, 1994.
 520. Peterson, B. Z., C. D. DeMaria, J. P. Adelman, and D. T. Yue. Calmodulin is the Ca2+ sensor for Ca2+‐dependent inactivation of L‐type calcium channels. Neuron 22: 549–558, 1999.
 521. Pfaffinger, P. J., J. M. Martin, D. D. Hunter, N. M. Nathanson and B. Hille. GTP‐binding proteins couple cardiac muscarinic receptors to a K channel. Nature 315: 536–538, 1985.
 522. Prod'hom, B., D. Pietrobon, and P. Hess. Interactions of protons with single open L‐type calcium channels. J. Gen. Physiol. 94: 23–42, 1989.
 523. Puri, T. S., B. L. Gerhardstein, X. L. Zhao, M. B. Ladner, and M. M. Hosey. Differential effects of subunit interactions on protein kinase A‐ and C‐mediated phosphorylation of L‐type calcium channels. Biochemistry 36: 9605–9615, 1997.
 524. Qu, Y., D. L. Campbell, and H. C. Strauss. Modulation of L‐type Ca2+ current by extracellular ATP in ferret isolated right ventricular myocytes. J. Physiol. (Lond.) 471: 295–317, 1993.
 525. Qu, Y., D. L. Campbell, A. R. Whorton, and H. C. Strauss. Modulation of basal L‐type Ca2+ current by adenosine in ferret isolated right ventricular myocytes. J. Physiol. (Lond.) 471: 269–293, 1993.
 526. Qu, Y., J. C. Rogers, T. N. Tanada, W. A. Catterall, and T. Scheuer. Phosphorylation of S1505 in the cardiac Na+ channel inactivation gate is required for modulation by protein kinase C. J. Gen. Physiol. 108: 375–379, 1996.
 527. Quast, U. Potassium channel openers: pharmacological and clinical aspects. Fund. Clin. Pharmacol. 6: 279–293, 1992.
 528. Randall, W. C. Selective autonomic innervation of the heart. In Nervous Control of Cardiovascular Function, edited by W. C. Randall. New York: Oxford University Press, 1984: 46–67.
 529. Ravens, U., X‐L. Wang, and E. Wettwer. Alpha adrenoceptor stimulation reduces outward currents in rat ventricular myocytes. J. Pharmacol. Exp. Ther. 250: 364–379, 1989.
 530. Reber, W. R. and R. Weingart. Ungulate cardiac Purkinje fibres: the influence of intracellular pH on the electrical cell‐to‐cell coupling. J. Physiol. (Lond.) 328: 87–104, 1982.
 531. Rees, S. A., J. L. Vandenberg, A. R. Wright, A. Yoshida, and T. Powell. Cell swelling has differential effects on the rapid and slow components of delayed rectifier potassium current in guinea pig myocytes. J. Gen. Physiol. 106: 1151–1170, 1995.
 532. Reuter, H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature 301: 569–574, 1983.
 533. Reuveny, E., P. A. Slesinger, J. Inglese, J. M. Morales, J. A. Iniquez‐Lluhi, R. J. Lefkowitz, H. R. Bourne, Y. N. Jan and L. Y. Jan. Activation of the cloned muscarinic potassium channel by G protein β γ subunits. Nature 370: 143–146, 1994.
 534. Rhoads, A. R., and F. Friedberg. Sequence motifs for calmodulin recognition. FASEB J. 11: 331–340, 1997.
 535. Rigel, D. Effects of neuropeptides on heart rate in dogs: comparison of VIP, PHI, NPY, CGRP and NT. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H311–H317, 1988.
 536. Rogers, T. B., S. T. Gaa, and I. S. Allen. Identification and characterization of functional angiotensin II receptors on cultured heart myocytes. J. Pharmacol. Exp. Ther. 236: 638–644, 1986.
 537. Rogg, H., A. Schmid and M. de Gasparo. Identification and characterization of angiotensin II receptor subtypes in rabbit ventricular myocardium. Biochem. Biophys. Res. Commun. 173: 416–422, 1990.
 538. Romanin, C., J.‐O. Karlsson and H. Schindler. Activity of cardiac L‐type Ca2+ channels is sensitive to cytoplasmic calcium. Pflugers Arch. 421: 516–518, 1992.
 539. Roos, A. and W. Boron. Intracellular pH. Physiol. Rev. 61: 296–434, 1981.
 540. Rossie, S., D. Gordon and W. A. Catterall. Identification of an intracellular domain of the sodium channel having multiple cAMP‐dependent phosphorylation sites. J. Biol. Chem. 262: 17530–17535, 1987.
 541. Rougier, O., G. Vassort, D. Garnier, Y‐M. Gargouil and E. Coraboeuf. Existence and role of a slow inward current during the frog atrial action potential. Pflugers Arch. 308: 91–110, 1969.
 542. Rubenstein, I. and O. Binah. Thyroid hormone modulates membrane currents in guinea pig ventricular myocytes. N‐S. Arch. Pharmacol. 340: 705–711, 1989.
 543. Ruknuden, A., F. Sachs and J. O. Bustamante. Stretch‐activated ion channels in tissue‐cultured chick heart. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H960–H972, 1993.
 544. Ruskoaho, H. Atrial natriuretic peptide: Synthesis, release, and metabolism. Pharmacol. Rev. 44: 479–602, 1992.
 545. Sachs, F. Mechanical transduction by ion channels: how forces reach the channel. Soc. Gen. Physiol. Ser. 52: 209–211, 1997.
 546. Sackman, B., A. Noma and W. Trautwein. Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammarian heart. Nature 303: 250–253, 1983.
 547. Sadoshima, J., and S. Izumo. The cellular and molecular responses of cardiac myocytes to mechanical stress. Annu Rev Physiol. 59: 551–571, 1997.
 548. Saint, D. A., Y.‐K. Ju, and P. W. Gage. A persistent sodium current in rat ventricular myocytes. J. Physiol. (Lond.) 453: 219–231, 1992.
 549. Sakaguchi, Y., G. Cui, and L. Sen. Acute effects of thyroid hormone on inward rectifier potassium channel currents in guinea pig ventricular myocytes. Endocrinology 137: 4744–4751, 1996.
 550. Sakura, H., C. Ammala, P. A. Smith, F. M. Gribble, and F. M. Ashcroft. Cloning and functional expression of the cDNA encoding a novel ATP‐sensitive potassium channel subunit expressed in pancreatic β‐cells, brain, heart and skeletal muscle. FEBS Lett. 377: 338–344, 1995.
 551. Sanders, R., R. J. Myerburg, H. Gelband, and A. I. Bassett. Dissimilar length‐tension relations of canine ventricular muscle and false tendon: electrophysiologic alterations accompanying deformation. J. Mol. Cell. Cardiol. 11: 209–219, 1979.
 552. Sanguinetti, M. C., M. E. Curran, A. Zou, J. Shen, P. S. Spector, D. L. Atkinson, and M. T. Keating. Coassembly of KvLQT1 and minK (Isk) proteins to form cardiac Iks potassium channel. Nature 384: 80–83, 1996.
 553. Sanguinetti, M. C. and N. K. Jurkiewicz. Two components of cardiac delayed rectifier K+ current: differential sensitivity to block by class III antiarrhythmic agents. J. Gen. Physiol. 96: 195–215, 1990.
 554. Sanguinetti, M. C. and N. K. Jurkiewicz. Isoproterenol antagonizes prolongation of refractory period by the class III antiarrhythmic agent, E‐4031 in guinea pig myocytes: mechanism of action. Circ. Res. 68: 77–84, 1991.
 555. Sanguinetti, M. C., C. Liang, M. E. Curran, and M. T. Keating. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the Ikr potassium channel. Cell 81: 299–307, 1995.
 556. Sano, T. and T. Sawanobori. Abnormal automaticity in canine Purkinje fibers focally subjected to low external concentrations of calcium. Circ. Res. 31: 158–164, 1972.
 557. Santana, L. F., A. M. Gomez, and W. J. Lederer. Ca2+ flux through promiscuous cardiac Na+ channels: slip‐mode conductance. Science 279: 1027–1033, 1998.
 558. Sasaki, N., T. Mitsuiye, and A. Noma. Increase of the delayed rectifier K+ and Na+‐K+ pump currents by hypotonic solutions in guinea pig cardiac myocytes. Circ. Res. 75: 887–895, 1994.
 559. Sato, R., A. Noma, Y. Kurachi, and H. Irisawa. Effects of intracellular acidification on membrane currents in ventricular cells of the guinea pig. Circ. Res. 57: 553–561, 1985.
 560. Satoh, H. Modulation of the automaticity by histamine and cimetidine in rabbit sino‐atrial node cells. Gen. Pharmacol. 24: 1213–1222, 1993.
 561. Satoh, H. and I. Seyama. On the mechanism by which changes in extracellular pH affect the electrical activity of the rabbit sino‐atrial node. J. Physiol. (Lond.) 381: 181–191, 1986.
 562. Scamps, F. and E. Carmeliet. Delayed K+ current and external K+ in single cardiac Purkinje cells. Am. J. Physiol. 257 (Cell Physiol. 16): C1086–C1092, 1989.
 563. Scamps, F., V. Rybin, M. Puceatu, V. Tkachuk, and G. Vassort. A Gs protein couples P2‐puringeric stimulation to cardiac Ca channels without cyclic AMP production. J. Gen. Physiol. 100: 675–701, 1992.
 564. Scamps, F. and G. Vassort. Mechanism of extracellular ATP‐induced depolarization of rat ventricular myocytes. Pflugers Arch. 417: 309–316, 1990.
 565. Scamps, F., and G. Vassort. Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells. Br. J. Pharmacol. 113: 982–986, 1994.
 566. Schaffer, S. W., C. Ballard‐Croft, S. Boerth, and S. N. Allo. Mechanisms underlying depressed Na+/Ca2+ exchanger activity in the diabetic heart. Cardiovasc. Res. 34: 129–136, 1997.
 567. Schaffer, S. W., and M. Mozaffari. Abnormal mechanical function in diabetes: relation to myocardial calcium handling. Co‐ron. Artery Dis. 7: 109–115, 1996.
 568. Schakow, T. E. and R. E. Ten Eick. Enhancement of ATP‐sensitive potassium current in cat ventricular myocytes by β‐adrenergic stimulation. J. Physiol. (Lond.) 474: 131–145, 1994.
 569. Scherer, R. W., C. F. Lo, and G. E. Breitwieser. Leukotriene C4 modulation of muscarinic K+ current in bulfrog atrial myocytes. J. Gen. Physiol. 102: 125–141, 1993.
 570. Schimerlik, M. I. Structure and regulation of muscarinic receptors. Annu. Rev. Physiol. 51: 217–227, 1989.
 571. Schoemaker, I. E., A. L. Meuelemans, L. J. Andries, and D. L. Brutsaert. Role of endocardial endothelium in positive inotropic action of vasopressin. Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H1148–H1151, 1990.
 572. Schreibmayer, W., B. Frohnwieser, N. Dascal, D. Platzer, R. Spreitzer, R. G. Kallen, and H. A. Lester. β‐Adrenergic modulation of currents by rat cardiac Na+ channels expressed in Xenopus laevis oocytes. Receptors Channels 2: 339–350, 1994.
 573. Schryock, J. C. and L. Belardinelli. Adenosine and adenosine receptors in the cardiovascular system: biochemistry, physiology, and pharmacology. Am. J. Cardiol. 79 (12A): 2–10, 1997.
 574. Schuba, L. M., T. Ogura and T. F. McDonald. Kinetic evidence distinguishing volume‐sensitive chloride current from other types in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 491: 69–80, 1996.
 575. Schubert, B., A. M. J. Vandongen, G. Kirsch, and A. M. Brown. Inhibition of cardiac Na currents by isoproterenol. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H977–H982, 1990.
 576. Segal, J., S. Masalha, H. Schwalb, G. Merin, J. B. Borman, and G. Uretzky. Acute effect of thyroid hormone in the rat heart: role of calcium. J. Endocrinol. 149: 73–80, 1996.
 577. Seifen, E., H. Schaer, and J. M. Marshall. Effects of calcium on the membrane potentials of single pacemaker fibers and atrial fibers in isolated rabbit atria. Nature 202: 1223–1224, 1964.
 578. Shah, A., I. S. Cohen, and M. Rosen. Stimulation of cardiac alpha receptors increases Na/K pump current and decreases GK via a pertussis toxin‐sensitive pathway. Biophys. J. 54: 219–225, 1988.
 579. Share, L. Role of vasopressin in cardiovascular regulation. Physiol. Rev. 68: 1248–1284, 1988.
 580. Sharma, V. K., H. M. Colecraft, D. X. Wang, A. I. Levey, E. V. Grigorenko, H. H. Yeh, and S.‐S. Sheu. Molecular and functional identification of m1 muscarinic acetylcholone receptors in rat ventricular myocytes. Circ. Res. 79: 86–93, 1996.
 581. Sharp, N., D. S. Neel, and R. L. Parsons. Influence of thyroid hormone levels on the electrical and mechanical properties of rabbit pappilary muscle. J. Mol. Cell. Cardiol. 17: 119–132, 1985.
 582. Sheets, M. F. and D. A. Hanck. Mechanism of extracellular divalent and trivalent cation block of the sodium current in canine cardiac Purkinje cell. J. Physiol. (Lond.) 454: 299–320, 1992.
 583. Sheets, M. F., D. A. Hanck, and H. A. Fozzard. Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells. Circ. Res. 63: 386–398, 1988.
 584. Shen, W. K., R. T. Tung, M. M. Machulda and Y. Kurachi. Essential role of nucleotide diphosphates in nicorandil‐medicated activation of cardiac ATP‐sensitive K+ channels. Circ. Res. 69: 1152–1158, 1991.
 585. Sheu, S.‐S., M. Korth, D. Lathrop, and H. A. Fozzard. Intraand extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac Purkinje strands. Circ. Res. 47: 692–700, 1980.
 586. Shibasaki, T. Conductance and kinetics of delayed rectifier channels in nodal cells of the rabbit heart. J. Physiol. (Lond.) 387: 227–250, 1987.
 587. Shibata, E. F. and W. R. Giles. Ionic currents which generate the spontaneous disatolic depolarization in individual cardiac pacemaker cells. Proc. Natl. Acad. Sci. U.S.A. 82: 7796–7800, 1985.
 588. Shimoni, Y., H. Banno, and R. B. Clark. Hyperthyroidism selectively modified a transient potassium current in rabbit ventricular and atrial myocytes. J. Physiol. (Lond.) 457: 369–389, 1992.
 589. Shimoni, Y., H. S. Ewart, and D. Severson. Type I and II models of diabetes produce different modifications of K+ currents in rat heart: role of insulin. J. Physiol. (Lond.) 507: 485–496, 1998.
 590. Shimoni, Y., L. Firek, D. Sverson, and W. Giles. Short‐term diabetes alters K+ currents in rat ventricular myocytes. Circ. Res. 74: 620–628, 1994.
 591. Shimoni, Y., C. Fiset, R. B. Clark, J. E. Dixon, D. McKinnon, and W. R. Giles. Thyroid hormone regulates postnatal expression of transient K+ channel isoforms in rat ventricle. J. Physiol. (Lond.) 500: 65–73, 1997.
 592. Shimoni, Y., D. Sverson, and W. Giles. Thyroid status and diabetes modulate regional differences in potassium currents in rat ventricle. J. Physiol. (Lond.) 488: 673–688, 1995.
 593. Shindo, T., M. Yamada, S. Isomoto, Y. Horio, and Y. Kurachi. SUR2 subtype (A and B)‐dependent differential activation of the cloned ATP‐sensitive K+ channels by pinacidil and nicor‐andil. Br. J. Physiol. 124: 985–991, 1998.
 594. Shistik, E., T. Ivanina, Y. Blumenstein, and N. Dascal. Crucial role of N terminus in function of cardiac L‐type Ca2+ channel and its modulation by protein kinase C. J. Biol. Chem. 273: 17901–17909, 1998.
 595. Shouten, V. J. A. and H. E. D. J. Ter Keurs. The slow repolarization phase of the action potential in rat heart. J. Physiol. (Lond.) 360: 13–25, 1985.
 596. Shryock, J., Y. Song, D. Wang, S. P. Baker, R. A. Olsson, and L. Belardinelli. Selective A2‐adenosine receptor agonists do not alter action potential duration, twitch shortening, or cyclic AMP accumulation in guinea‐pig, rat, or rabbit isolated ventricular myocytes. Circ. Res. 72: 194–205, 1993.
 597. Shyng, S., T. Ferrigni, and C. G. Nichols. Regulation of KATP channel activity by diazoxide and MgADP. Distinct functions of the two nucleotide binding folds of the sulfonylurea receptor. J. Gen. Physiol. 110: 643–654, 1997.
 598. Shyng, S. L. and C. G. Nichols. Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282: 1138–1141, 1998.
 599. Shui, Z., M. R. Boyett, W.‐J. Zang, T. Haga, and K. Kameyama. Receptor kinase‐dependent desensitization of the muscarinic K+ current in rat atrial cells. J. Physiol. (Lond.) 487: 359–366, 1995.
 600. Sigurdson, W. J., C. E. Morris, B. L. Brezden, and D. R. Gardner. Stretch activation of a K+ channel in molluscan heart cells. J. Exp. Biol. 127: 191–209, 1987.
 601. Simpson, P. C. Proto‐oncogenes and cardiac hypertrophy. Annu. Rev. Physiol. 51: 189–202, 1988.
 602. Singer‐Lahat, D., I. Lotan, M. Biel, V. Flockerzi, F. Hofmann, and N. Dascal. Cardiac calcium channels expressed in Xenopus oocytes are modulated by dephosphorylation but not by cAMP‐dependent phosphorylation. Receptors Channels 2: 215–226, 1994.
 603. Sipido, K. R., G. Callewaert, and E. Carmeliet. [Ca2+]i transients and [CA2+]i‐dependent chloride current in single Purkinje cells from rabbit heart. J. Physiol. (Lond.). 468: 641–667, 1993.
 604. Soejima, M. and A. Noma. Mode of regulation of the ACh‐sensitive K‐channel by the muscarinic receptor in rabbit atrial cells. Pflugers Arch. 400: 424–431, 1984.
 605. Soldatov, N. M., R. D. Zuhlke, A. Bouron, and H. Reuter. Molecular structures involved in L‐type calcium channel inactiva‐tion. Role of the carboxyl‐terminal region encoded by exon 40–42 in α1C subunit in the kinetics and Ca2+‐dependent inactivation. J. Biol. Chem. 272: 3560–3566, 1997.
 606. Song, Y., S. Thedford, B. B. Lerman, and L. Belardinelli. Adenosine‐sensitive afterdepolarizations and triggered activity in guinea pig ventricular myocytes. Circ. Res. 70: 743–753, 1992.
 607. Sorbera, L. A. and M. Morad. Atrionatriuretic peptide transforms cardiac sodium channels into calcium‐conducting channels. Science 252: 449–452, 1991.
 608. Sorota, S. Swelling‐induced chloride‐sensitive current in canine atrial cells revealed by whole‐cell patch‐clamp method. Circ. Res. 70: 679–687, 1992.
 609. Sorota, S., Y. Tsuji, T. Tajima, and A. J. Pappano. Pertussis toxin treatment blocks hyperpolarization by muscarinic agonists in chick atrium. Circ. Res. 57: 748–758, 1985.
 610. Sperelakis, N. Origin of the cardiac resting potential. In: Handbook of Physiology. Section II: The Cardiovascular System, edited by R. M. Berne, N. Sperelakis, and S. R. Geiger. Bethesda, MD:, American Physiological Society, 1979: 187–267.
 611. Spindler, A. J., S. J. Noble, D. Noble, and J. Y. LeGuennec. The effects of sodium substitution on currents determining the resting potential in guinea‐pig ventricular cell. Exp. Physiol. 83: 121–136, 1998.
 612. Standen, N. B., J. M. Quayle, N. W. Davies, J. E. Brayden, Y. Huang, and M. T. Nelson. Hyperpolarizing vasodilators activate ATP‐sensitive K channels in arterial smooth muscle. Science 245: 177–180, 1989.
 613. Standen, N. B. and P. R. Stanfield. A potential‐and time‐dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. J. Physiol. (Lond.) 380: 169–191, 1978.
 614. Stein, B., W. Schmitz, H. Scholz, and C. Seeland. Pharmacological characterization of A2‐adenosine receptors in guinea‐pig ventricular cardiomyocytes. J. Mol. Cell. Cardiol. 26: 403–414, 1994.
 615. Stengl, M., E. Carmeliet, K. Mubagwa, and W. Flameng. Modulation of transient outward current by extracellular protons and Cd2+ in rat and human ventricular myocytes. J. Physiol. (Lond.) 511: 827–836, 1998.
 616. Stobrawa, S. M., T. Breiderhoff, S. Takamori, D. Engel, M. Schweizer, A. A. Zdebik, M. R. Bosl, K. Ruether, H. Jahn, A. Draguhn, R. Jahn, and T. J. Jentsch. Disruption of ClC‐3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29: 185–196, 2001.
 617. Strickler, J., K. A. Jakobson, and B. T. Liang. Direct preconditioning of cultured chick ventricular myocytes. J. Clin. Invest. 98: 1773–1779, 1996.
 618. Sui, J. L., K. W. Chan, and D. E. Logothetis. Na+ activation of the muscarinic K+ channel by a G‐protein‐independent mechanism. J. Gen. Physiol. 108: 381–391, 1996.
 619. Suleymanian, M. A. and C. M. Baumgarten. Osmotic gradient‐induced water permeation across the sarcolemma of rabbit ventricular myocytes. J. Gen. Physiol. 107: 503–514, 1996.
 620. Sunami, A., Z. Fan, F. Nakamura, M. Naka, T. Tanaka, T. Sawanobori, and M. Hiraoka. The catalytic subunit of cyclic AMP‐dependent protein kinase directly inhibits sodium channel activities in guinea‐pig ventricular myocytes. Pflugers Arch. 419: 415–417, 1991.
 621. Tajima, T., Y. Tsuji, J. H. Brown, and A. J. Pappano. Pertussis toxin‐insensitive phosphoinositide hydrolysis, membrane depolarization, and positive inotropic effect of carbachol in chick atria. Circ. Res. 61: 436–445, 1987.
 622. Takano, M., D. Qin, and A. Noma. ATP‐dependent decay and recovery of K+ channels in guinea pig cardiac myocytes. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H45–H50, 1990.
 623. Tanaka, H., Y. Habuchi, T. Yamamoto, M. Nishio, J. Morikawa, and M. Yoshimura. Negative chronotropic actions of endothelin‐1 on rabbit sinoatrial node pacemaker cells. Br. J. Pharmacol. 122: 321–329, 1997.
 624. Tareen, F. M., A. Yoshida, and K. Ono. Modulation of beta‐adrenergic responses of chrolide and calcium currents by external cations in guinea‐pig ventricular cells. J. Physiol. (Lond). 457: 211–228, 1992.
 625. Tarr, M., J. W. Trank, and K. K. Goertz. Intracellular magnesium affects IK in single frog atrial cells. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1663–H1669, 1989.
 626. Terai, T., T. Furukawa, Y. Katayama, and M. Hiraoka. Effects of external acidosis on HERG current expressed in Xenopus oocytes. J. Mol. Cell. Cardiol. 32: 11–21, 2000.
 627. Terzic, A., A. Jahangir, and Y. Kurachi. Cardiac ATP‐sensitive K+ channels: regulation by intracellular nucleotides and K+ channel opening drugs. Am. J. Physiol. 269 (Cell Physiol. 38): C525–C545, 1995.
 628. Terzic, A., M. Puceat, G. Vassort, and S. M. Vogel. Cardiac α1‐adrenoceptors: an overview. Pharmacol. Rev. 45: 147–175, 1993.
 629. Terzic, A., R. T. Tung, A. Inanobe, T. Katada, and Y. Kurachi. G proteins activate ATP‐sensitive K+ channels by antagonizing the ATP‐dependent gating. Neuron 12: 885–893, 1994.
 630. Thomas, G. P., S. M. Sim, and M. Karmazyn. Differential effects of endothelin‐1 on basal and isoprenaline‐enhanced Ca2+ current in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 503: 55–65, 1997.
 631. Thome, U., F. Berga, U. Borchard, and D. Hafner. Electrophysiological characterization of histamine receptor subtypes in sheep cardiac Purkinje fibers. Agents Actions 37: 30–38, 1992.
 632. Thornton, J. D., G. S. Liu, R. A. Olsson, and J. M. Downey. Intravenous pretreatment with A1‐selective adenosine analogues protects the heart against infarction. Circulation 85: 650–665, 1992.
 633. Thornton, J. D., C. S. Thornton, D. L. Sterling, and J. M. Downey. Blockade of ATP‐sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts. Circ. Res. 72: 44–49, 1993.
 634. Toda, N. and T. C. West. The action of ouabain on the function of the atrioventricular node in rabbits. J. Pharmacol. Exp. Ther. 169: 287–297, 1970.
 635. Tohse, N. Calcium‐sensitive delayed rectifier potassium current in guinea pig ventricular cells. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H1200–H1207, 1990.
 636. Tohse, N., Y. Hattori, H. Nakaya, M. Endou, and M. Kanno. Inability of endothelin to increase Ca2+ current in guinea‐pig heart cells. Br. J. Pharmacol. 99: 437–438, 1990.
 637. Tohse, N., M. Kameyama, and H. Irisawa. Intracellular Ca2+ and protein kinase C modulate K+ current in guinea pig heart cells. Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H1321–1324, 1987.
 638. Tohse, N., H. Nakaya, Y. Hattori, M. Endou, and M. Kanno. Inhibitory effect mediated by α1‐adrenoceptors on transient outward current in isolated rat ventricular cells. Pflugers Arch. 415: 575–581, 1990.
 639. Tohse, N., H. Nakaya, and M. Kanno. α1‐Adrenoceptor stimulation enhances the delayed rectifier K+ current of guinea‐pig ventricular cells through activation of protein kinase C. Circ. Res. 71: 1441–1446, 1992.
 640. Tohse, N., H. Nakaya, Y. Takeda, and M. Kanno. Cyclic GMP‐mediated inhibition of L‐type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells. Br. J. Pharmacol. 114: 1076–1082, 1995.
 641. Townsend, C. and R. Horn. Effect of alkali metal cations on slow inactivation of cardiac Na+ channels. J. Gen. Physiol. 110: 23–33, 1997.
 642. Trautwein, W. and J. Dudel. Aktionpotential und Mechano‐gramm des Katzen‐pappillarmuskels als Funktion der Temper‐atur. Pflugers Arch. 260: 104–115, 1954.
 643. Trautwein, W., J. Taniguchi, and A. Norma. The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. Pflugers Arch. 392: 307–314, 1982.
 644. Trudeau, M. C., J. W. Warmke, B. Ganetzky, and G. A. Robertson. HERG, a human inward rectifier in the voltage‐gated potassium channel family. Science 269: 92–95, 1995.
 645. Tseng, G. N. Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium. Circ. Res. 63: 468–482, 1988.
 646. Tseng, G. N. Cell swelling increases membrane conductance of canine cardiac cells: evidence for a volume‐sensitive Cl channel. Am. J. Physiol. 262 (Cell Physiol. 31): C1056–C1068, 1992.
 647. Tseng, G. N. and P. A. Boyden. Multiple types of Ca2+ currents in single canine Purkinje cells. Circ. Res. 65: 1735–1750, 1989.
 648. Tsien, R. W., B. P. Bean, P. Hess, J. B. Lansman, B. Nilius, and M. C. Norwicky. Mechanisms of calcium channel modulation by β‐adrenergic agents and dihydropyridine Ca agonists. J. Mol. Cell. Cardiol. 18: 691–710, 1986.
 649. Tsuchida, K., H. Watajima, and S. Otomo. Calcium current in rat diabetic ventricular myocytes. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): H2280–H2289, 1994.
 650. Tucker, S. J., F. M. Grible, C. Zhao, S. Trapp, and F. M. Ashcroft. Truncation of Kir6.2 produces ATP‐sensitive K+ channels in the absence of the sulfonylurea receptor. Nature 387: 179–183, 1997.
 651. Tung, R. T. and Y. Kurachi. On the mechanism of nucleotide diphosphate activation of the ATP‐sensitive K+ channel in ventricular cell of guinea‐pig. J. Physiol. (Lond.) 437: 239–256, 1991.
 652. Tytgart, J., B. Nilius, and E. Carmeliet. Modulation of the T‐type cardiac Ca channel by changes in proton concentration. J. Gen. Physiol. 96: 973–990, 1990.
 653. Van Calker, D., M. Muller, and B. Hamprecht. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. J. Neurochem. 33: 999–1005, 1979.
 654. Vandenberg, C. A. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc. Natl. Acad. Sci. U.S.A. 84: 2560–2564, 1987.
 655. Vandenberg, J. L., S. A. Rees, A. R. Wright, and T. Powell. Cell swelling and ion transport pathways in cardiac myocytes. Car‐diovasc. Res. 1996; 32: 85–97.
 656. Vandenberg, J. I., A. Yoshida, K. Kirk, and T. Powell. Swelling‐activated and isoprenaline‐activated chloride currents in guinea pig cardiac myocytes have distinct electrophysiology and pharmacology. J. Gen. Physiol. 104: 997–1017, 1994.
 657. Van Ginneken, A. C. G. and W. R. Giles. Voltage clamp measurements of the hyperpolarization‐activated current If in single cells from rabbit sino‐atrial node. J. Physiol. (Lond.) 434: 57–83, 1991.
 658. Van Wagoner, D. R. Mechanosensitive gating of atrial ATP‐sensitive potassium channels. Circ. Res. 72: 973–983, 1993.
 659. Varnum, M. D., A. E. Busch, C. T. Bond, J. Maylie, and J. P. Adelman. The min K channel underlies the cardiac potassium current Iks and mediates species‐specific responses to protein kinase C. Proc. Natl. Acad. Sci. U.S.A. 90: 11528–11532, 1993.
 660. Vassalle, M., K. Greenspan, S. Jomain, and B. F. Hoffmann. Effects of potassium on automaticity and conduction of canine hearts. Am. J. Physiol. 207: 334–340, 1964.
 661. Vaughan‐Jones, R. D. Chloride activity and its control in skeletal and cardiac muscle. Phil. Trans. R. Soc. Lond. B. Biol, Sci. 299: 537–548, 1982.
 662. Vaughan‐Jones, R. D. and M.‐L. Wu. Extracellular H+ inactivation of Na+‐H+ exchange in the sheep cardiac Purkinje fibre. J. Physiol. (Lond.) 428: 441–466, 1990.
 663. Vaxelaire, J.‐F., S. Laurent, P. Lacolley, V. Briand, H. Schmitt, and J. B. Michel. Atrial natriuretic peptide decreases contractility of cultured chick ventricular cells. Life Sci. 45: 41–48, 1989.
 664. Vereecke, J. and E. Carmeliet. Sr action potentials in cardiac Purkinje fibres. II. Dependence of the Sr conductance on the external Sr concentration and Sr‐Ca antagonism. Pflugers Arch. 322: 73–82, 1971.
 665. Verheijck, E. E., A. C. van Ginneken, J. Bourier, and L. N. Bouman. Effects of delayed rectifier current blockade by E‐4031 on impulse generation in single sinoatrial nodal myocytes of the rabbit. Circ. Res. 76: 607–615, 1995.
 666. Visentin, S., A. Zaza, A. Ferroni, C. Tromba, and D. Di‐Francesco. Sodium current block caused by group‐IIb cations in calf Purkinje fibres and in guinea‐pig ventricular myocytes. Pflugers Arch. 417: 213–222, 1990.
 667. Wahler, G. M. Developmental increase in the inwardly rectifying potassium current of rat ventricular myocytes. Am. J. Physiol. 262 (Cell. Physiol. 31): C1266–C1272, 1992.
 668. Walker, B. R., M. E. Childs, and E. M. Adams. Direct cardiac effects of vasopressin: role of V1‐ and V2‐vasopressinergic receptors. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H261–H265, 1988.
 669. Walsh, K. B. Activation of a heart chloride conductance during stimulation of protein kinase C. Mol. Pharmacol. 40: 342–346, 1991.
 670. Walsh, K. B., T. B. Begenisich, and R. S. Kass. β‐Adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents. J. Gen. Physiol. 93: 841–854, 1989.
 671. Walsh, K. B. and R. S. Kass. Regulation of a heart potassium channel by protein A and C. Science 242: 67–69, 1988.
 672. Walsh, K. B. and K. J. Long. Properties of a protein kinase C‐activated chloride current in guinea pig ventricular myocytes. Circ. Res. 74: 121–129, 1994.
 673. Wang, D. W., T. Kiyosue, S. Shigematsu, and M. Arita. Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes. Am. J. Physiol. 269 (Heart Circ. Physiol. 38): H1288–H1296, 1995.
 674. Wang, S., M. J. Morales, S. Liu, H. C. Straus, and R. L. Rasmusson. Time, voltage and ionic concentration dependence of rectification of h‐erg expressed in Xenopus oocytes. FEBS Lett. 389: 167–173, 1996.
 675. Wang, X. L., E. Wettwer, G. Gross, and U. Ravens. Reduction of cardiac outward currents by alpha1‐adrenoceptor stimulation: a subtype specific effect. J. Pharmacol. Exp. Ther. 259: 783–788, 1991.
 676. Wang, Y. G. and S. L. Lipsius. Acetylcholine activates a glibenclamide‐sensitive K+ current in cat atrial myocytes. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1322–H1334, 1995.
 677. Wang, Y. G., and S. L. Lipsius. Acetylcholine elicits a rebound stimulation of Ca2+ current mediated by pertussis toxin‐sensitive G protein and cAMP‐dependent protein kinase A in atrial myocytes. Circ. Res. 76: 634–644, 1995.
 678. Wang, Z., T. Kimitsuki, and A. Noma. Conductance properties of the Na+‐activated K+ channel in guinea‐pig ventricular cells. J. Physiol. (Lond.) 433: 241–257, 1991.
 679. Watanabe, A. M. and H. R. Besch. Interaction between cyclic adenosine monophosphate and cyclic guanosine monophosphate in guinea pig ventricular myocardium. Circ. Res. 37: 309–317, 1975.
 680. Watanabe, Y. and L. S. Dreifus. Electrophysiological effects of digitalis on A‐V transmission. Am. J. Physiol. 211: 1461–1466, 1966.
 681. Watanabe, Y., T. Noda, and Y. Habuchi. Effect of cardiac glycosides on AV nodal impulse formation and conduction. In Electrophysiology of the Sinoatrial and Atrioventricular Nodes. edited by T. Mazgalev, L. F. Dreifus, and E. L. Michelson. New York: Alan R. Liss, 1988: 111–131.
 682. Watson, C. L. and M. R. Gold. Effect of intracellular and extracellular acidosis on sodium current in ventricular myocytes. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1749–H1756, 1995.
 683. Weidmann, S. The effect of the cardiac membrane potential on the rapid availability of the sodium‐carrying system. J. Physiol. (Lond.) 127: 213–224, 1955.
 684. Weidmann, S. Effects of calcium ions and local anesthetics on electrical properties of Purkinje fibres. J. Physiol. (Lond.) 129: 568–582, 1955.
 685. Weidmann, S. Shortening of the cardiac action potential due to a brief injection of KCl following the onset of activity. J. Physiol. (Lond.) 132: 157–163, 1956.
 686. Wendt, D. J., C. F. Starmer, and A. O. Grant. pH dependence of kinetics and steady‐state block of cardiac sodium channels by lidocaine. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H1588–H1598, 1993.
 687. West, G. A. and L. Belardinelli. Correlation of sinus slowing and hyperpolarization caused by adenosine in sinus node. Pfiugers Arch. 403: 75–81, 1985.
 688. Westfall, D. P., K. O. Sedaa, K. Shinozuka, R. A. Bjur, and I. L. Buxton. ATP as a cotransmitter. Ann. N.Y. Acad. Sci. 603: 300–310, 1990.
 689. Whalley, D. W., L. C. Hool, R. W. Ten Eick, and H. H. Rasmussen. Effect of osmotic swelling and shrinkage on Na+‐K+ pump activity in mammalian cardiac myocytes. Am. J. Physiol. 265 (Cell Physiol. 34): C1201–C1210, 1993.
 690. Whalley, D. W., D. J. Wendt, C. F. Starmer, Y. Rudy, and A. O. Grant. Voltage‐independent effects of extracellular K+ on the Na+ current and phase 0 of the action potential in isolated cardiac myocytes. Circ. Res. 75: 491–502, 1994.
 691. White, R. E. and H. C. Hartzell. Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes. Science 239: 778–780, 1988.
 692. Wible, B. A., M. Taglialata, E. Ficker, and A. M. Brown. Gating of inwardly rectifying K+ channels localized to a single negatively charged residue. Nature 371: 246–249, 1994.
 693. Wibo, M., O. Feron, L. Zheng, M. Maleki, F. Kolar, and T. Goodfraind. Thyroid status and postnatal changes in sub‐sarcolemmal distribution and isoform expression of rat cardiac dihydropyridine receptors. Cardiovasc. Res. 37: 151–159, 1998.
 694. Wickenden, A. D., R. Kaprielian, T. G. Parker, O. T. Jones, and P. H. Backx. Effects of development and thyroid hormone on K+ currents and K+ channel gene expression in rat ventricle. J. Physiol. (Lond.) 504: 271–286, 1997.
 695. Wickman, K. D., J. A. Inigues‐Lluhi, P. A. Davenport, R. Taussig, G. B. Crapivinsky, M. E. Linder, A. G. Gilman, and D. E. Clapham. Recombinant G‐protein βγ subunits activate the muscarinic‐gated atrial potassium channel. Nature 368: 255–257, 1994.
 696. Wiechen, K., D. T. Yue, and S. Herzig. Two distinct functional effects of protein phosphatase inhibitors on guinea‐pig cardiac L‐type Ca2+ channels. J. Physiol. (Lond.) 484: 583–592, 1995.
 697. Wiggins, J. R. and P. F. Cranefield. The effect on membrane potential and electrical activity of adding sodium to sodium‐depleted cardiac Purkinje fibers. J. Gen. Physiol. 64: 473–493, 1974.
 698. Wilde, A. A. M., D. Escande, C. A. Schumacher, D. Thuringer, M. Mestre, J. W. T. Fiolet, and M. J. Janse. Potassium accumulation in the globally ischemic mammalian heart. A role for the ATP‐sensitive potassium channel. Circ. Res. 67: 835–843, 1990.
 699. Wilde, A. A. M. and M. J. Janse. Electrophysiological effects of ATP‐sensitive potassium channel modulation: implications for arrhythmogenesis. Cardiovasc. Res. 28: 16–24, 1994.
 700. Wolff, A. A. and R. Levi. Histamine and cardiac arrhythmias. Circ. Res. 58: 1–16, 1986.
 701. Woodbury, L. A. and H. H. Hecht. Effects of cardiac glycosides upon the electrical activity of single ventricular fibers of the frog heart, and their relation to the digitalis effect of the electrocardiogram. Circulation 6: 172–182, 1952.
 702. Woodbury, L. A., H. H. Hecht, and A. R. Christopherson. Membrane resting and action potentials of single cardiac muscle fibers of the frog ventricle. Am. J. Physiol. 164: 307–318, 1951.
 703. Xie, L‐H., M. Horie, A. F. James, M. Watanuki, and S. Sasayama. Endothelin‐1 inhibits L‐type Ca current enhanced by isoproterenol in guinea‐pig ventricular myocytes. Pflugers Arch. 431: 533–539, 1996.
 704. Xie, L‐H., M. Takano, and A. Noma. Development of inwardly rectifying K+ channel family in rat ventricular myocytes. Am. J. Physiol. 272 (Heart Circ. Physiol. 41): H1741–H1750, 1997.
 705. Xu, D., H. Kong, and B. T. Liang. Expression and pharmacological characterization of a stimulatory subtype of adenosine receptor in fetal chick ventricular myocytes. Circ. Res. 70: 56–65, 1992.
 706. Xu, Y. J. and V. Gopalakarishnan. Vasopressin increases cytosolic free [Ca2+] in the neonatal rat cardiomyocyte: evidence for V1 subtype receptors. Circ. Res. 69: 239–245, 1991.
 707. Xu, Z., and G. J. Rozanski. Proton inhibition of transient outward potassium current in rat ventricular myocytes. J. Mol. Cell. Cardiol. 29: 481–490, 1997.
 708. Yamaoka, K., and I. Seyama. Regulation of Ca channel by intracellular Ca2+ and Mg2+ in frog ventricular cells. Pflugers Arch. 431: 305–317, 1996.
 709. Yamawake, N., Y. Hirano, T. Sawanobori, and M. Hiraoka. Arrhythmogenic effects of isoproterenol‐activated Cl current in guinea‐pig ventricular myocytes. J. Mol. Cell. Cardiol. 24: 1047–1058, 1992.
 710. Yanagisawa, M., H. Kurihara, S. Kimura, Y. Tomobe, M. Kobayashi, Y. Mitsui, Y. Yazaki, K. Goto, and T. Masaki. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415, 1988.
 711. Yang, T., D. J. Snyders, and D. M. Roden. Rapid inactivation determines the rectification and [K+]o dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ. Res. 80: 782–789, 1997.
 712. Yao, Z., I. Cavero, and G. J. Gross. Activation of cardiac KATP channels: an endogenous protective mechanism during repetitive ischemia. Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H495–H504, 1993.
 713. Yao, Z. and G. J. Gross. Glibenclamide antagonizes adenosine A1 receptor‐mediated cardioprotection in stunned myocardium. Circulation 88: 235–244, 1993.
 714. Yatani, A., A. M. Brown, and N. Akaike. Effect of extracellular pH on sodium current in isolated, single rat ventricular cells. J. Membr. Biol. 78: 163–168, 1984.
 715. Yatani, A., K. Okabe, J. Codina, A. Bimbaumer, and A. M. Brown. Heart rate regulation by G protein acting on the cardiac pacemaker channel. Science 249: 1163–1166, 1990.
 716. Yazawa, K. and Y. Abiko. Modulation by histamine of the delayed outward potassium current in guinea‐pig ventricular myocytes. Br. J. Pharmacol. 109: 142–147, 1993.
 717. Yazawa, K. and M. Kameyama. Mechanisms of receptor‐mediated modulation of the delayed outward potassium current in guinea‐pig ventricular myocytes. J. Physiol. (Lond.) 421: 135–150, 1990.
 718. Yoshimoto, K., Y. Hattori, H. Houzen, M. Kanno, and K. Yasuda. Histamine H1‐receptor‐mediated increase in Ca2+ transient without a change in the Ca2+ current in electrically stimulated guinea‐pig atrial myocytes. Br. J. Pharmacol. 124: 1744–1750, 1998.
 719. Yu, H., D. McKinnon, J. E. Dixon, J. Gao, R. Wymore, I. S. Cohen. P. Danilo, Jr., A. Shvilkin, E. P. Anyukovsky, E. A. Sosunov, M. Hara, and M. R. Rosen. Transient outward current, Ito1 is altered in cardiac memory. Circulation 99: 1898–1905, 1999.
 720. Yue, D. T., P. H. Backx, and J. P. Imredy. Calcium‐sensitive in‐activation in the gating of single calcium channels. Science 250: 1735–1738, 1990.
 721. Yue, D. T., S. Herzig, and E. Marban. β‐Adrenergic stimulation of calcium channels occurs by potentiation of high‐activity gating modes. Proc. Natl. Acad. Sci. U.S.A. 87: 753–757, 1990.
 722. Zakharov, S. I., S. Pieramici, G. K. Kumar, N. R. Prabhakar, and R. D. Harvey. Nitric oxide synthase activity in guinea pig ventricular myocytes is not involved in muscarinic inhibition of cAMP‐regulated ion channels. Circ. Res. 78: 925–935, 1996.
 723. Zaza, A., R. P. Kline, and M. R. Rosen. Effects of α‐adrenergic stimulation on intracellular sodium activity and automaticity in canine Purkinje fibers. Circ. Res. 66: 416–426, 1990.
 724. Zaza, A., M. Rocchetti, and D. DiFrancesco. Modulation of the hyperpolarization‐activated current (If) by adenosine in rabbit sinoatrial myocytes. Circulation 94: 734–741, 1996.
 725. Zhang, J., T. H. Larsen, and M. Lieberman. F‐actin modulates swelling‐activated chloride current in cultured chick cardiac myocytes. Am. J. Physiol. 273 (Cell Physiol. 42): C1215–C1224, 1997.
 726. Zhang, J. and S. A. Siegelbaum. Effects of external protons on single cardiac sodium channels from guinea pig ventricular myocytes. J. Gen. Physiol. 98: 1065–1083, 1991.
 727. Zhang, K., P. L. Barrington, R. L. Martin, and R. E. Ten Eick. Protein kinase‐dependent Cl− currents in feline ventricular myocytes. Circ. Res. 75: 133–143, 1994.
 728. Zhang, S., Y. Hirano, and M. Hiraoka. Arginine vasopressin‐induced potentiation of unitary L‐type Ca2+ channel current in guinea pig ventricular myocytes. Circ. Res. 76: 592–599, 1995.
 729. Zhang, S., M. Hiraoka, and Y. Hirano. Effects of α1,‐adrenergic stimulation on L‐type Ca2+ current in rat ventricular myocytes. J. Mol. Cell. Cardiol. 30: 1955–1965, 1998.
 730. Zhang, S., T. Sawanobori, H. Adaniya, Y. Hirano, and M. Hiraoka. Dual effects of external magnesium on action potential duration in guinea pig ventricular myocytes. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H2321–H2328, 1995.
 731. Zheng, J.‐S., A. Christie, M. N. Levy, and A. Scarpa. Modulation by extracellular ATP of two distinct currents in rat myocytes. Am. J. Physiol. 264 (Cell Physiol. 33): C1411–C1417, 1993.
 732. Zong, X., J. Schreieck, G. Mehrke, A. Welling, A. Schuster, E. Bosse, V. Flockerzi, and F. Hofmann. On the regulation of the expressed L‐type calcium channel by cAMP‐dependent phosphorylation. Pflugers Arch. 430: 340–347, 1995.
 733. Zuhlke, R. D. and H. Reuter. Ca2+‐sensitive inactivation of L‐type‐Ca2+ channels depends on multiple cytoplasmic amino acid sequences of the α1c subunit. Proc. Natl. Acad. Sci. U.S.A. 95: 3287–3294, 1998.
 734. Zuhlke, R. D. G., S. Pitt, K. Deisseroth, R. W. Tsien, and H. Reuter. Calmodulin supports both inactivation and facilitation of L‐type calcium channels. Nature 399: 159–162, 1999.
 735. Zygmunt, A. C. Intracellular calcium activates a chloride current in canine ventricular myocytes. Am. J. Physiol. 267 (Heart Circ. Physiol. 36): H1984–H1995, 1994.
 736. Zygmunt, A. C. and W. R. Gibbons. Calcium‐activated chloride current in rabbit ventricular myocytes. Circ. Res. 68: 424–437, 1991.
 737. Zygmunt, A. C. and W. R. Gibbons. Properties of calcium‐activated chloride current in the heart. J. Gen. Physiol. 99: 391–414, 1992.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Modulation of Electrical Properties by Ions, Hormones, and Drugs
 

How to Cite

Masayasu Hiraoka. Modulation of Electrical Properties by Ions, Hormones, and Drugs. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 595-653. First published in print 2002. doi: 10.1002/cphy.cp020116