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Neuromuscular transmission in intramural blood vessels

G. D. S. Hirst

10.1002/cphy.cp060145

Source: Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Organization and Structure of Intramural Blood Vessels
2 Innervation of Intramural Blood Vessels
3 Passive Electrical Properties of Submucosal Arterioles
3.1 Resting Potential
3.2 Electrical Coupling Between Arteriolar Smooth Muscle Cells
3.3 Summary
4 Neuromuscular Transmission in Arterioles
5 Responses of Submucosal Arterioles to Sympathetic Nerve Stimulation
6 Analysis of Excitatory Junction Potentials
6.1 Time Course
6.2 Quantal Content
6.3 Summary
7 Initiation of Contraction in Submucosal Arterioles
7.1 Potential‐Dependent Calcium Entry
7.2 Receptor‐Activated Tension Development
7.3 Summary
8 Integration in Submucosal Arterioles
9 Pharmacology of Excitatory Junction Potentials
9.1 Identity of Transmitter Responsible for Initiation of Excitatory Junction Potentials
10 Summary and Future Directions
Figure 1. Figure 1.

Micrographs of submucosal arteriole of guinea pig ileum viewed with conventional optics showing submucosal arterioles that were dissected from a segment of guinea pig ileum. An arteriole with ∼50‐μm diam runs diagonally across micrographs; finer branch at proximal end is visible in right corner. Arteriole has wall thickness of ∼5 μm, which is less than that of red blood cells remaining in vessel lumen in A. B shows the same vessel during maintained sympathetic nerve stimulation. Calibration bar, 30 μm.

From Hirst 74
Figure 2. Figure 2.

Micrographs showing sympathetic innervation of submucosal arteriole of guinea pig. Preparation was fixed and viewed with Falck‐Hillarp technique, which demonstrates catecholamine‐containing nerves. Two plates are of same segment of arteriolar tree: one is focused on luminal surface and other on inner surface of arteriole. Bundles of brightly fluorescent axons and single beaded axons can be seen wrapped around arteriole. Calibration bar, μm. 50 μm.

Micrography courtesy of E. M. MacLachlan
Figure 3. Figure 3.

Electron micrograph of sympathetic nerve varicosity. Figure shows varicosity in apposition with 2 submucosal arteriolar smooth muscle cells. Arrow, basal laminae of 1 smooth muscle cell and varicosity are fused. In this section and adjacent ones separation between nerve and muscle was 60 μm. Note abundant small granular vesicles, mitochondria, and occasional large granular vesicle. Calibration bar, 0.5 μm.

Micrograph courtesy of S. Luff.
Figure 4. Figure 4.

Reconstruction of 2 different varicosities. Figure illustrates small (upper) and averaged‐sized (lower) varicosity. Figure prepared by computer superimpositions of successive electron micrographs. Dotted lines, membranes of varicosities seen in sequential sections; crosses, positions of synaptic vesicles; solid shading, areas of fusion of basal laminae, where thickening of these areas reflect undulations in areas of contact rather than variations in cleft width; solid lines, sections of arteriolar muscle membrane. Larger varicosity has a larger area of contact and contains more vesicles. In both, vesicles are concentrated toward regions of apposition with underlying smooth muscle layer. Calibration bar, 1.0 μm. (Micrograph courtesy of S. Luff and E. M. MacLachlan.)
Figure 5. Figure 5.

Drawing of lower varicosity shown in Fig. 4. For clarity only 1 neuronal membrane has been shown. Open circles, small granular vesicles. Vesicles are connected toward region of fused basal lamellae. Varicosity is en passant; terminal axons can be seen originating on either side of junctional swelling. Calibration bar, 0.5 μm.
Figure 6. Figure 6.

Relationship between membrane potential of submucosal arterioles and external potassium concentration. Closed circles, membrane potentials of submucosal arterioles measured in different extracellular potassium concentrations; solid line, relationship between membrane potential and potassium concentration predicted by Goldman‐Hodgkin‐Katz equation with permeability ratios PK+:PCl‐:PNa+ assumed to be 1:0.09:0.005; dashed line, Nernst prediction for relationship with an intracellular potassium concentration of 120 mM. Fit between Goldman‐Hodgkin‐Katz prediction and experimental data is good for external potassium concentrations in range of 4 to 80 mM. At concentrations <4 mM a marked difference between predicted and observed relationships is apparent.

From Hirst and van Helden 86
Figure 7. Figure 7.

Relationship between membrane resistance and external potassium concentration. Closed circles, membrane resistances (Rm) of submucosal arterioles [expressed as a ratio of resistance in test potassium to resistance in control potassium (5 mM)], which were determined in different extracellular potassium concentrations. Dashed line, crossing a ratio of unity (solid line), is relationship between membrane resistance and potassium concentration predicted by Goldman‐Hodgkin‐Katz equation. Similar to Fig. 6 there is a marked divergence between predicted and observed curves at extracellular potassium concentrations <4 mM.

From Hirst and van Helden 86
Figure 8. Figure 8.

Electrical coupling between arteriolar smooth muscle cells. Two independent intracellular recording electrodes were inserted into separate branches of same arteriolar tree with total separation of 580 μm. When current (1 nA) was passed through 1 electrode a membrane potential change was detected at other electrode. Potential change (upper trace) was not detected if same current was passed through current‐passing electrode after just withdrawing it from arteriolar smooth muscle layer.

From Hirst and Neild 80
Figure 9. Figure 9.

Passive electrical properties of 1.4‐mm segment of arteriole. One electrode, used to inject current, was inserted in center of preparation and second electrode, used for recording membrane potential, was inserted toward one end of arteriole. Short and long current pulses were injected and resultant membrane potential changes, along with excitatory junction potentials evoked by transmural stimulation, were recorded. Data are plotted in the right half of figure. Time course of decay of 3 potential changes is the same, and each can be described by a single exponential. These data can be used to determine passive electrical properties of arteriole (for further details, see ref. 80.

From Hirst and Neild 80
Figure 10. Figure 10.

Membrane potential changes recorded from submucosal arteriole in responses to perivascular nerve stimulation. Traces show membrane potential changes produced by 1, 3 (10 Hz), 4 (10 Hz), and 5 stimuli (20 Hz). Excitatory junction potential, initiated by single stimulus, has time to peak of ∼100 ms and total duration of ∼1 s. With large number of stimuli, junctional depolarization exceeded threshold and initiated action potentials with rapid and plateau components. Arteriolar constriction was only detected if an action potential had been first initiated.

From Hirst 74
Figure 11. Figure 11.

Relationship between amplitude of excitatory junction potentials (EJPs) recorded from 2 different arterioles and stimulus strength applied to perivascular nerves. As strength is increased, amplitude of EJPs increases up to a maximum value. Relationships are not smooth, indicating that each arteriole is innervated by a number of fibers, each of a different threshold. Presumably finer vessel was innervated by 3 fibers and larger by 5 fibers.

From Hirst 74
Figure 12. Figure 12.

Time course of junctional current (open circles) derived from time course of excitatory junction potential (closed circles) and arteriolar passive electrical properties. Current time was calculated using equation suggested by Curtis and Eccles 37, which assumes that the segment of arteriole is isopotential during current flow. Current reaches peak after 10 ms and then decays to 0 within a further 200 ms. More prolonged time course of excitatory junction potential reflects long membrane time constant of arteriolar smooth muscle membrane.

From Hirst and Neild 80
Figure 13. Figure 13.

Comparison between excitatory junctional current (EJC) and excitatory junction potential (EJP) that it produces. EJP was recorded in voltage‐recording mode; EJC was recorded in single‐electrode voltage‐clamp mode. Decay of both can be described by single exponentials: time constant of decay of EJP was 485 ms and that of EJC was 47 ms.

From Hirst et al. 76
Figure 14. Figure 14.

Effect of membrane potential on excitatory junctional current (EJC) amplitude and time course. A: current records allow comparison between amplitude of EJC recorded at holding potential of −60 mV with those recorded during voltage‐clamp steps to −40 mV and −115 mV. At depolarized potential, current amplitude is reduced, and at hyperpolarized level, amplitude is increased. B: plots of time courses of these 3 junctional currents: time course of decay of each is very similar. Rise time of EJC is slowed because of filtering (100 Hz) to improve signal‐to‐noise ratio.

From Finkel et al. 47
Figure 15. Figure 15.

Recordings from short segment of arteriole during train of low‐frequency, supramaximal transmural stimuli. Arrows, successive excitatory junction potentials (EJPs) fluctuate in amplitude but not time course. Spontaneous EJPs (SEJPs), with a similar time course, occurred at irregular intervals during recording period. Only a few SEJPs would have to be released synchronously to generate an EJP

From Hirst and Neild 81
Figure 16. Figure 16.

Voltage‐clamp recording from short segment of arteriole during train of low‐frequency, supramaximal transmural stimuli; 6 successive records of membrane current (holding potential −60 mV) are shown. Closed circles, stimuli were given. Successive excitatory junctional currents (EJCs) fluctuated in amplitude and on one occasion failed to release. Spontaneous EJCs (SEJCs) are also shown as irregularly occurring inward currents; again their amplitudes are only slightly smaller than those evoked currents. SEJCs had peak amplitudes of 0.1–0.2 nA.

From Finkel et al. 47
Figure 17. Figure 17.

Regenerative membrane potential changes initiated in rat cerebral arterioles. Each record was made from same short segment of arteriole and shows membrane potential changes produced by injecting depolarizing currents. A: control solution; a small regenerative potential change is superimposed on depolarizing potential change. B: after addition of tetraethylammonium chloride (TEA; 10 mM), depolarization now produced larger amplitude regenerative potential changes. C: duration of depolarizing pulse was shortened and 2‐component action potential was readily distinguished. D: action potential had rapid component and slower plateau component each of which persisted in presence of tetrodotoxin (TTX; 1 × 10−6 M). E: control response obtained before addition of manganese ions. F: both components were abolished by substitution of calcium ions by manganese ions.

From Hirst et al. 85
Figure 18. Figure 18.

Integrals of inward calcium currents in cerebral arterioles. When segments of arteriole were voltage clamped and their potentials stepped to depolarized potentials, 2 distinct inward currents were detected. Small depolarizations resulted in a small‐amplitude, noninactivating current; with larger depolarizations a rapidly inactivating component was superimposed on noninactivating current. Integrals of current flowing through low‐threshold, noninactivating current (open circles) and high‐threshold, inactivating current (closed circles) are plotted as function of membrane potential. Charge increases smoothly as function of depolarization.

From Hirst et al. 85
Figure 19. Figure 19.

Comparison between membrane potential changes and arteriolar diameter changes produced by repetitive nerve stimulation and superfusion of norepinephrine [noradrenaline (NA)]. A: perivascular nerves were stimulated repetitively to produce maintained depolarization of ∼7 mV; stimulus strength was adjusted so only 1 or 2 nerve fibers were stimulated and to prevent initiation of suprathreshold membrane potential change. This potential change did not lead to constriction. B: in contrast, a threshold concentration of norepinephrine (1 × 10−6 M) caused membrane potential to become “noisy” but produced a constriction. Both responses to norepinephrine unlike responses to sympathetic nerve stimulation, were abolished by phentolamine or prazosin.
Figure 20. Figure 20.

Calculations of membrane potential changes that occur in blood vessels of different sizes during repetitive asynchronous sympathetic nerve activity. A: rabbit ear artery (diam 150 μm); B: arteriole of guinea pig submucosa (diam 50 μm). Sustained but irregular potential changes occur in both vessels and in finer vessel, at a given frequency of stimulation, membrane potential change is larger.

From Neild 132
Figure 21. Figure 21.

Membrane potential changes produced by ionophoretic application of norepinephrine. A: records were produced by 2 pulses of norepinephrine (duration 10 ms, 40 and 50 nA, respectively); B: records produced by similar pulses after adding phentolamine (3 × 10−5 M) to physiological saline. Both responses persist and a spontaneous excitatory junction potential is also seen.
Figure 22. Figure 22.

Junctional localization of positions where norepinephrine produces receptor activation. Trace A shows membrane potential response produced by ionophoretic application of norepinephrine. Traces B and C show lack of membrane potential changes when electrode position was varied. D: map of distribution of sympathetic nerve fibers. Open circles, positions at which depolarizing responses were detected; closed circles, points where membrane potential changes were not detected. All “hot spots” were subsequently found to be within 10 μm of a fluorescent nerve.

From Hirst and Neild 83
Figure 23. Figure 23.

Activation of γ‐receptors by bath‐applied norepinephrine [noradrenaline (NA)]. Records were made from a submucosal arteriole in presence of prazosin (1 × 10−6 M). Norepinephrine was applied by superfusion. Note high concentration of norepinephrine required to activate receptors; similar responses were detected in lower concentrations of prazosin, suggesting that responses do not result from activation of receptors.
Figure 24. Figure 24.

Diagram of neural control system in submucosal arteriole. Figure shows sympathetic varicosity containing small granular vesicles (open circles; s.g.v.); vesicles are concentrated toward region of apposition (shaded area) between varicosity and underlying smooth muscle cell. Individual smooth muscle cells are electrically coupled to neighboring cells by low‐resistance electrical contacts (gap junction); resulting syncytium forms neuroeffector target. In junctional cleft, specialized receptors to norepinephrine are located (γ‐receptors), which when activated allow an influx of sodium ions and an efflux of potassium ions. Resulting depolarization causes opening of voltage‐dependent calcium channels (hexagon), leading to calcium entry from extracellular fluid. In contrast, α‐receptors, which have an extrajunctional location, when activated by norepinephrine, lead to increase in internal calcium concentration by discharging a bound store.


Figure 1.

Micrographs of submucosal arteriole of guinea pig ileum viewed with conventional optics showing submucosal arterioles that were dissected from a segment of guinea pig ileum. An arteriole with ∼50‐μm diam runs diagonally across micrographs; finer branch at proximal end is visible in right corner. Arteriole has wall thickness of ∼5 μm, which is less than that of red blood cells remaining in vessel lumen in A. B shows the same vessel during maintained sympathetic nerve stimulation. Calibration bar, 30 μm.

From Hirst 74


Figure 2.

Micrographs showing sympathetic innervation of submucosal arteriole of guinea pig. Preparation was fixed and viewed with Falck‐Hillarp technique, which demonstrates catecholamine‐containing nerves. Two plates are of same segment of arteriolar tree: one is focused on luminal surface and other on inner surface of arteriole. Bundles of brightly fluorescent axons and single beaded axons can be seen wrapped around arteriole. Calibration bar, μm. 50 μm.

Micrography courtesy of E. M. MacLachlan


Figure 3.

Electron micrograph of sympathetic nerve varicosity. Figure shows varicosity in apposition with 2 submucosal arteriolar smooth muscle cells. Arrow, basal laminae of 1 smooth muscle cell and varicosity are fused. In this section and adjacent ones separation between nerve and muscle was 60 μm. Note abundant small granular vesicles, mitochondria, and occasional large granular vesicle. Calibration bar, 0.5 μm.

Micrograph courtesy of S. Luff.


Figure 4.

Reconstruction of 2 different varicosities. Figure illustrates small (upper) and averaged‐sized (lower) varicosity. Figure prepared by computer superimpositions of successive electron micrographs. Dotted lines, membranes of varicosities seen in sequential sections; crosses, positions of synaptic vesicles; solid shading, areas of fusion of basal laminae, where thickening of these areas reflect undulations in areas of contact rather than variations in cleft width; solid lines, sections of arteriolar muscle membrane. Larger varicosity has a larger area of contact and contains more vesicles. In both, vesicles are concentrated toward regions of apposition with underlying smooth muscle layer. Calibration bar, 1.0 μm. (Micrograph courtesy of S. Luff and E. M. MacLachlan.)



Figure 5.

Drawing of lower varicosity shown in Fig. 4. For clarity only 1 neuronal membrane has been shown. Open circles, small granular vesicles. Vesicles are connected toward region of fused basal lamellae. Varicosity is en passant; terminal axons can be seen originating on either side of junctional swelling. Calibration bar, 0.5 μm.



Figure 6.

Relationship between membrane potential of submucosal arterioles and external potassium concentration. Closed circles, membrane potentials of submucosal arterioles measured in different extracellular potassium concentrations; solid line, relationship between membrane potential and potassium concentration predicted by Goldman‐Hodgkin‐Katz equation with permeability ratios PK+:PCl‐:PNa+ assumed to be 1:0.09:0.005; dashed line, Nernst prediction for relationship with an intracellular potassium concentration of 120 mM. Fit between Goldman‐Hodgkin‐Katz prediction and experimental data is good for external potassium concentrations in range of 4 to 80 mM. At concentrations <4 mM a marked difference between predicted and observed relationships is apparent.

From Hirst and van Helden 86


Figure 7.

Relationship between membrane resistance and external potassium concentration. Closed circles, membrane resistances (Rm) of submucosal arterioles [expressed as a ratio of resistance in test potassium to resistance in control potassium (5 mM)], which were determined in different extracellular potassium concentrations. Dashed line, crossing a ratio of unity (solid line), is relationship between membrane resistance and potassium concentration predicted by Goldman‐Hodgkin‐Katz equation. Similar to Fig. 6 there is a marked divergence between predicted and observed curves at extracellular potassium concentrations <4 mM.

From Hirst and van Helden 86


Figure 8.

Electrical coupling between arteriolar smooth muscle cells. Two independent intracellular recording electrodes were inserted into separate branches of same arteriolar tree with total separation of 580 μm. When current (1 nA) was passed through 1 electrode a membrane potential change was detected at other electrode. Potential change (upper trace) was not detected if same current was passed through current‐passing electrode after just withdrawing it from arteriolar smooth muscle layer.

From Hirst and Neild 80


Figure 9.

Passive electrical properties of 1.4‐mm segment of arteriole. One electrode, used to inject current, was inserted in center of preparation and second electrode, used for recording membrane potential, was inserted toward one end of arteriole. Short and long current pulses were injected and resultant membrane potential changes, along with excitatory junction potentials evoked by transmural stimulation, were recorded. Data are plotted in the right half of figure. Time course of decay of 3 potential changes is the same, and each can be described by a single exponential. These data can be used to determine passive electrical properties of arteriole (for further details, see ref. 80.

From Hirst and Neild 80


Figure 10.

Membrane potential changes recorded from submucosal arteriole in responses to perivascular nerve stimulation. Traces show membrane potential changes produced by 1, 3 (10 Hz), 4 (10 Hz), and 5 stimuli (20 Hz). Excitatory junction potential, initiated by single stimulus, has time to peak of ∼100 ms and total duration of ∼1 s. With large number of stimuli, junctional depolarization exceeded threshold and initiated action potentials with rapid and plateau components. Arteriolar constriction was only detected if an action potential had been first initiated.

From Hirst 74


Figure 11.

Relationship between amplitude of excitatory junction potentials (EJPs) recorded from 2 different arterioles and stimulus strength applied to perivascular nerves. As strength is increased, amplitude of EJPs increases up to a maximum value. Relationships are not smooth, indicating that each arteriole is innervated by a number of fibers, each of a different threshold. Presumably finer vessel was innervated by 3 fibers and larger by 5 fibers.

From Hirst 74


Figure 12.

Time course of junctional current (open circles) derived from time course of excitatory junction potential (closed circles) and arteriolar passive electrical properties. Current time was calculated using equation suggested by Curtis and Eccles 37, which assumes that the segment of arteriole is isopotential during current flow. Current reaches peak after 10 ms and then decays to 0 within a further 200 ms. More prolonged time course of excitatory junction potential reflects long membrane time constant of arteriolar smooth muscle membrane.

From Hirst and Neild 80


Figure 13.

Comparison between excitatory junctional current (EJC) and excitatory junction potential (EJP) that it produces. EJP was recorded in voltage‐recording mode; EJC was recorded in single‐electrode voltage‐clamp mode. Decay of both can be described by single exponentials: time constant of decay of EJP was 485 ms and that of EJC was 47 ms.

From Hirst et al. 76


Figure 14.

Effect of membrane potential on excitatory junctional current (EJC) amplitude and time course. A: current records allow comparison between amplitude of EJC recorded at holding potential of −60 mV with those recorded during voltage‐clamp steps to −40 mV and −115 mV. At depolarized potential, current amplitude is reduced, and at hyperpolarized level, amplitude is increased. B: plots of time courses of these 3 junctional currents: time course of decay of each is very similar. Rise time of EJC is slowed because of filtering (100 Hz) to improve signal‐to‐noise ratio.

From Finkel et al. 47


Figure 15.

Recordings from short segment of arteriole during train of low‐frequency, supramaximal transmural stimuli. Arrows, successive excitatory junction potentials (EJPs) fluctuate in amplitude but not time course. Spontaneous EJPs (SEJPs), with a similar time course, occurred at irregular intervals during recording period. Only a few SEJPs would have to be released synchronously to generate an EJP

From Hirst and Neild 81


Figure 16.

Voltage‐clamp recording from short segment of arteriole during train of low‐frequency, supramaximal transmural stimuli; 6 successive records of membrane current (holding potential −60 mV) are shown. Closed circles, stimuli were given. Successive excitatory junctional currents (EJCs) fluctuated in amplitude and on one occasion failed to release. Spontaneous EJCs (SEJCs) are also shown as irregularly occurring inward currents; again their amplitudes are only slightly smaller than those evoked currents. SEJCs had peak amplitudes of 0.1–0.2 nA.

From Finkel et al. 47


Figure 17.

Regenerative membrane potential changes initiated in rat cerebral arterioles. Each record was made from same short segment of arteriole and shows membrane potential changes produced by injecting depolarizing currents. A: control solution; a small regenerative potential change is superimposed on depolarizing potential change. B: after addition of tetraethylammonium chloride (TEA; 10 mM), depolarization now produced larger amplitude regenerative potential changes. C: duration of depolarizing pulse was shortened and 2‐component action potential was readily distinguished. D: action potential had rapid component and slower plateau component each of which persisted in presence of tetrodotoxin (TTX; 1 × 10−6 M). E: control response obtained before addition of manganese ions. F: both components were abolished by substitution of calcium ions by manganese ions.

From Hirst et al. 85


Figure 18.

Integrals of inward calcium currents in cerebral arterioles. When segments of arteriole were voltage clamped and their potentials stepped to depolarized potentials, 2 distinct inward currents were detected. Small depolarizations resulted in a small‐amplitude, noninactivating current; with larger depolarizations a rapidly inactivating component was superimposed on noninactivating current. Integrals of current flowing through low‐threshold, noninactivating current (open circles) and high‐threshold, inactivating current (closed circles) are plotted as function of membrane potential. Charge increases smoothly as function of depolarization.

From Hirst et al. 85


Figure 19.

Comparison between membrane potential changes and arteriolar diameter changes produced by repetitive nerve stimulation and superfusion of norepinephrine [noradrenaline (NA)]. A: perivascular nerves were stimulated repetitively to produce maintained depolarization of ∼7 mV; stimulus strength was adjusted so only 1 or 2 nerve fibers were stimulated and to prevent initiation of suprathreshold membrane potential change. This potential change did not lead to constriction. B: in contrast, a threshold concentration of norepinephrine (1 × 10−6 M) caused membrane potential to become “noisy” but produced a constriction. Both responses to norepinephrine unlike responses to sympathetic nerve stimulation, were abolished by phentolamine or prazosin.



Figure 20.

Calculations of membrane potential changes that occur in blood vessels of different sizes during repetitive asynchronous sympathetic nerve activity. A: rabbit ear artery (diam 150 μm); B: arteriole of guinea pig submucosa (diam 50 μm). Sustained but irregular potential changes occur in both vessels and in finer vessel, at a given frequency of stimulation, membrane potential change is larger.

From Neild 132


Figure 21.

Membrane potential changes produced by ionophoretic application of norepinephrine. A: records were produced by 2 pulses of norepinephrine (duration 10 ms, 40 and 50 nA, respectively); B: records produced by similar pulses after adding phentolamine (3 × 10−5 M) to physiological saline. Both responses persist and a spontaneous excitatory junction potential is also seen.



Figure 22.

Junctional localization of positions where norepinephrine produces receptor activation. Trace A shows membrane potential response produced by ionophoretic application of norepinephrine. Traces B and C show lack of membrane potential changes when electrode position was varied. D: map of distribution of sympathetic nerve fibers. Open circles, positions at which depolarizing responses were detected; closed circles, points where membrane potential changes were not detected. All “hot spots” were subsequently found to be within 10 μm of a fluorescent nerve.

From Hirst and Neild 83


Figure 23.

Activation of γ‐receptors by bath‐applied norepinephrine [noradrenaline (NA)]. Records were made from a submucosal arteriole in presence of prazosin (1 × 10−6 M). Norepinephrine was applied by superfusion. Note high concentration of norepinephrine required to activate receptors; similar responses were detected in lower concentrations of prazosin, suggesting that responses do not result from activation of receptors.



Figure 24.

Diagram of neural control system in submucosal arteriole. Figure shows sympathetic varicosity containing small granular vesicles (open circles; s.g.v.); vesicles are concentrated toward region of apposition (shaded area) between varicosity and underlying smooth muscle cell. Individual smooth muscle cells are electrically coupled to neighboring cells by low‐resistance electrical contacts (gap junction); resulting syncytium forms neuroeffector target. In junctional cleft, specialized receptors to norepinephrine are located (γ‐receptors), which when activated allow an influx of sodium ions and an efflux of potassium ions. Resulting depolarization causes opening of voltage‐dependent calcium channels (hexagon), leading to calcium entry from extracellular fluid. In contrast, α‐receptors, which have an extrajunctional location, when activated by norepinephrine, lead to increase in internal calcium concentration by discharging a bound store.

References
 1. Abe, Y., and T. Tomita. Cable properties of smooth muscle. J. Physiol. Lond. 214: 173–190, 1968.
 2. Aickin, C. C., A. F. Brading, and T. V. Burgyga. Evidence for sodium‐calcium exchange on the guinea‐pig ureter. J. Physiol. Lond. 347: 411–430, 1984.
 3. Ambache, N., and M. A. Zar. Evidence against adrenergic motor transmission in the guinea‐pig vas deferens. J. Physiol. Lond. 216: 359–389, 1971.
 4. Angus, J. A., and R. M. Brazenor. Relaxation of large coronary artery by verapamil, D600 and nifedipine is constrictor sensitive: comparison with glycerol trinitrate. J. Cardiovasc. Pharmacol. 5: 321–328, 1983.
 5. Bell, C. Transmission from vasoconstrictor and vasodilator nerves to single muscle cells of the guinea‐pig uterine artery. J. Physiol. Lond. 205: 695–708, 1969.
 6. Bell, C. Comparison of the antagonist effects of phentolamine on vasoconstrictor responses to exogenous and neurally released noradrenaline in vivo. Br. J. Pharmacol. 85: 249–253, 1985.
 7. Bell, C., and M. Vogt. Release of endogenous noradrenaline from an isolated muscular artery. J. Physiol. Lond. 215: 509–520, 1971.
 8. Bennett, M. R. Autonomic Neuromuscular Transmission. Cambridge, UK: Cambridge Univ. Press, 1972.
 9. Bennett, M. R., and J. Middleton. An electrophysiological analysis of the effects of amine‐uptake blockers and α‐adrenoceptor blockers on adrenergic neuromuscular transmission. Br. J. Pharmacol. 55: 87–95, 1975.
 10. Bevan, J. A., R. D. Bevan, and S. P. Duckles. Adrenergic regulation of vascular smooth muscle. In: Handbook of Physiology. The Cardiovascular System. Vascular Smooth Muscle, edited by D. F. Bohr, A. P. Somlyo, and H. V. Sparks, Jr. Bethesda, MD: Am. Physiol. Soc., 1980, sect. 2, vol. II, chapt. 13, p. 515–566.
 11. Biber, B., J. Fara, and O. Lundgren. Intestinal vasodilation response to transmural electrical stimulation. Acta. Physiol. Scand. Suppl. 87: 277–282, 1973.
 12. Blakeley, A. G. H., D. A. Brown, T. C. Cunnane, A. M. French, J. C. McGrath, and N. C. Scott. Effects of nifedipine on electrical and mechanical responses of rat and guinea‐pig vas deferens. Nature Lond. 294: 759–761, 1981.
 13. Blakeley, A. G. H., and T. C. Cunnane. The packeted release of transmitter from the sympathetic nerves of the guinea‐pig vas deferens: an electrophysiological study. J. Physiol. Lond. 296: 85–96, 1979.
 14. Bolton, T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol. Rev. 59: 606–718, 1979.
 15. Bolton, T. B., R. J. Lang, and T. Takewaki. Mechanisms of action of noradrenaline and carbachol on myometrial smooth muscle of guinea‐pig anterior mesenteric artery. J. Physiol. Lond. 351: 549–572, 1981.
 16. Bolton, T. B., and W. A. Large. Are junction potentials essential? Dual mechanism of smooth muscle cell activation by transmitter released from autonomic nerves. Q. J. Exp. Physiol. Cogn. Med. Sci. 71: 1–28, 1986.
 17. Brading, A. F. Ionic distribution and mechanisms of transmembrane ion movements in smooth muscle. In: Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 65–92.
 18. Bülbring, E., H. Ohashi, and T. Tomita. Adrenergic mechanisms. In: Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 219–248.
 19. Bülbring, E., and J. H. Szurszewski. The stimulant action of noradrenaline (α‐action) on guinea‐pig myometrium compared with that of acetylcholine. Proc. R. Soc. Lond. B Biol. Sci. 185: 225–262, 1974.
 20. Burnstock, G., and M. Costa. Adrenergic Neurones London: Chapman & Hall, 1975.
 21. Burnstock, G., and M. E. Holman. The transmission of excitation from autonomic nerve to smooth muscle. J. Physiol. Lond. 155: 115–133, 1961.
 22. Burnstock, G., and M. E. Holman. Spontaneous potentials at sympathetic nerve endings in smooth muscle. J. Physiol. Lond. 160: 446–460, 1962.
 23. Burnstock, G., and M. E. Holman. Effect of denervation and of reserpine treatment on transmission at sympathetic nerve endings. J. Physiol. Lond. 160: 461–469, 1962.
 24. Burnstock, G., and M. E. Holman. An electrophysiological investigation of the actions of some autonomic blocking drugs on transmission in the guinea‐pig vas deferens. Br. J. Pharmacol. 23: 600–612, 1964.
 25. Byrne, N. G., G. D. S. Hirst, and W. A. Large. Electrophysiological analysis of adrenoceptors in the rat basilar artery during development. Br. J. Pharmacol. 86: 217–227, 1985.
 26. Byrne, N. G., and W. A. Large. The effect of α,β‐methylene ATP on the depolarizations evoked by noradrenaline (γ‐response) and ATP in the immature rat basilar artery. Br. J. Pharmacol. 88: 6–8, 1986.
 27. Bywater, R. A. R., and G. S. Taylor. The passive membrane properties and excitatory junction potentials of the guinea‐pig vas deferens. J. Physiol. Lond. 300: 303–316, 1980.
 28. Casley‐Smith, J. R., and B. J. Gannon. Intestinal microcirculation: spatial organization and fine structure. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 9–32.
 29. Casteels, R. Membrane potential in smooth muscle cells. In: Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 105–126.
 30. Casteels, R., K. Kitamura, H. Kuryama, and H. Suzuki. The membrane properties of the smooth muscle cells of the. rabbit main pulmonary artery. J. Physiol. Lond. 271: 41–61, 1979.
 31. Casteels, R., K. Kitamura, H. Kuryama, and H. Suzuki. Excitation‐contraction coupling in the smooth muscle cells of the rabbit main pulmonary artery. J. Physiol. Lond. 271: 62–79, 1979.
 32. Cheung, D. W. Two components in the cellular response of the rat tail artery to nerve stimulation. J. Physiol. Lond. 328: 461–468, 1982.
 33. Cheung, D. W. Neural regulation of electrical and mechanical activities in the rat tail artery. Pfluegers Arch. 400: 335–357, 1984.
 34. Chubb, I. W. In: Synapses, edited by G. A. Cotterell and P. N. R. Usherwood. London: Blackie, 1977, p. 269–290.
 35. Cole, K. S. Membranes, Ions and Impulses: A Chapter of Classical Biophysics. Berkeley: Univ. of California Press, 1968.
 36. Cunnane, T. C., and L. Stjarne. Secretion of transmitter from individual varicosities of guinea‐pig and mouse vas deferens: all‐or‐none and extremely intermittent. Neuroscience 7: 2565–2576, 1982.
 37. Curtis, D. R., and J. C., Eccles. The time course of excitatory and inhibitory synaptic actions. J. Physiol. Lond. 145: 529–546, 1959.
 38. De Feo, T. T., and K. G. Morgan. Calcium force relationships as detected with aequorin in two different vascular smooth muscles of the ferret. J. Physiol. Lond. 369: 269–282, 1985.
 39. Devine, C. E., and F. O. Simpson. The fine structure of vascular sympathetic neuromuscular contacts in the rat. Am. J. Anat. 121: 153–174, 1967.
 40. Devine, C. E., A. V. Somlyo, and A. P. Somlyo. Sarcoplasmic reticulum and excitation‐contraction coupling in mammalian smooth muscles. J. Cell Biol. 52: 690–718, 1972.
 41. Donald, D. E. Splanchnic circulation. In: Handbook of Physiology. The Cardiovascular System. Peripheral Circulation, edited by J. T. Shepherd and F. M. Abboud. Bethesda, MD: Am. Physiol. Soc., 1983, sect. 2., vol. III, chapt. 13, p. 219–240.
 42. Droogmans, G., L. Raeymaekers, and R. Casteels. Electro‐ and pharmacochemical coupling in the smooth muscle cells of the rabbit ear artery. J. Gen. Physiol. 70: 129–148, 1977.
 43. Endo, M., T. Kitazawa, S. Yagi, M. Iino, and Y. Kikuta. Some properties of chemically skinned smooth muscle fibres. In: Excitation‐Contraction Coupling in Smooth Muscle, edited by R. Casteels, T. Godfraind, and J. C. Ruegg. Amsterdam: Elsevier/North‐Holland, 1984, p. 199–209.
 44. Falck, B., N.‐A. Hillarp, G. Thieme, and Torp. Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10: 348–354, 1962.
 45. Fara, J. W. Post prandial mesenteric hyperemia. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 99–106.
 46. Fedan, J. S., G. K. Hogaboom, J. P. O'Donnell, J. Colby, and D. P. Westfall. Contribution by purines to the neurogenic response of the vas deferens of the guinea‐pig. Eur. J. Pharmacol. 69: 41–53, 1981.
 47. Finkel, A. S., G. D. S. Hirst, and D. F. van Helden. Some properties of excitatory junction currents recorded from submucosal arterioles of guinea‐pig ileum. J. Physiol. Lond. 351: 87–98, 1984.
 48. Finkel, A. S., and S. J. Redman. The synaptic current evoked by impulses in single group 1a axons. J. Physiol. Lond. 342: 615–632, 1983.
 49. Flavahan, N. A., T. L. Grant, J. Greig, and J. C. Mc‐Grath. Analysis of alpha‐receptor mediated, and other, components in the sympathetic vasopressor responses of the pithed rat. Br. J. Pharmacol. 86: 265–274, 1985.
 50. Folkow, B., and E. Neil. Circulation. Oxford, UK: Oxford Univ. Press, 1971.
 51. Fondacaro, J. D. Intestinal blood flow and motility. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd, and D. N. Granger. New York: Raven, 1984, p. 107–120.
 52. Fried, G., H. Lagercrantz, R. Klein, and A. Thureson‐Klein. Large and small noradrenergic vesicles—origin, contents and functional significance. In: Catecholamines: Basic and Peripheral Mechanisms, edited by E. Usdin, A. Carlson, A. Dahlstrom, and J. Engel. New York: Liss, 1984, p. 45–53.
 53. Fujiwara, S., T. Itoh, and H. Suzuki. Membrane properties and excitatory neuromuscular transmission in the smooth muscle of dog cerebral arteries. Br. J. Pharmacol. 77: 447–455, 1982.
 54. Fujiwara, S., and H. Kuriyama. Nicardipine actions on smooth muscle cells and excitatory neuromuscular transmission in the guinea‐pig basilar artery. J. Pharmacol. Exp. Ther. 225: 447–455, 1983.
 55. Furchgott, R. F. The classification of adrenoceptors (adrenergic receptors). An evaluation from the stand point of receptor theory. In: Handbuch der Experimentellen Pharmakologie. Catecholamines, edited by H. Blaschko and H. Muscholl. New York: Springer‐Verlag, 1972, vol. 33, p. 283–335.
 56. Furness, J. B. Arrangement of blood vessels and their relation with adrenergic nerves in the rat mesentry. J. Anat. 115: 347–364, 1973.
 57. Furness, J. B., M. Costa, P. C. Emson, R. Håkanson, E. Moghimzadeh, F. Sundler, I. L. Taylor, and R. E. Chance. Distribution, pathways and reactions to drug treatment of nerves with neuropeptide Y and pancreatic polypeptide‐like immunoreactivity in the guinea‐pig digestive tract. Cell Tissue Res. 234: 71–92, 1983.
 58. Furness, J. B., M. Costa, I. L. Gibbins, I. J. Llewellyn‐Smith, and J. R. Oliver. Neurochemically similar myenteric and submucous neurons directly tracted to the mucosa of the small intestine. Cell Tissue Res. 241: 155–163, 1985.
 59. Furness, J. B., J. McLean, and G. Burnstock. Distribution of adrenergic nerves and changes in neuromuscular transmission in the mouse vas deferens during post‐natal development. Dev. Biol. 21: 491–505, 1970.
 60. Gabella, G. Structure of smooth muscles. In: Smooth Muscle: An Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 1–46.
 61. Gage, P. W. Generation of end‐plate potentials. Physiol. Rev. 56: 177–247, 1976.
 62. Geffen, L., and B. Jarrott. Cellular aspects of catecholaminergic neurons. In: Handbook of Physiology. The Nervous System, Cellular Biology of Neurons, edited by E. R. Kandell Bethesda, MD: Am. Physiol. Soc., 1977, sect. 1, vol. 1, pt. 1, chapt. 13, p. 521–571.
 63. Glick, G., S. E. Epstein, A. S. Wechsler, and E. Braunwald. Physiological differences between the effects of neuronally released and bloodborne norepinephrine on beta adrenergic receptors in the arterial bed of the dog. Circ. Res. 21: 217–227, 1985.
 64. Goldman, D. E. Potential, impedance and rectification in membranes. J. Gen. Physiol. 27: 37–60, 1968.
 65. Greenway, C. V. Neural control and autoregulatory escape. In: Physiology of the Intestinal Circulation, edited by A. P. Shepherd and D. N. Granger. New York: Raven, 1984, p. 61–72.
 66. Haeusler, G., and S. Thorens. Effects of tetraethylammonium chloride on contractile, membrane and cable properties of rabbit artery muscle. J. Physiol. Lond. 303: 203–224, 1980.
 67. Hendrickx, H., and R. Casteels. Electrogenic sodium pump in arterial smooth muscle cells. Pfluegers Arch. 346: 299–306, 1974.
 68. Hermsmeyer, K. Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension. Circ. Res. 38: 362–367, 1976.
 69. Hill, C. E., G. D. S. Hirst, M. C. Ngu, and D. F. van Helden. Sympathetic postganglionic reinnervation of mesenteric arteries and enteric neurones of the ileum of the rat. J. Auton. Nerv. Syst. 14: 317–334, 1985.
 70. Hill, C. E., G. D. S. Hirst, G. D. Silverberg, and D. F. van Helden. Sympathetic innervation and excitability of arterioles originating from the rat middle cerebral artery. J. Physiol. Lond. 371: 305–316, 1986.
 71. Hill, C. E., G. D. S. Hirst, and D. F. Helden. Development of the sympathetic innervation to proximal and distal arteries of the rat mesentry. J. Physiol. Lond. 338: 129–147, 1983.
 72. Hille, B. Ionic basis of resting and action potentials. In: Handbook of Physiology. The Nervous System. Cellular Biology of Neurons, edited by E. R. Kandell Bethesda, MD: Am. Physiol. Soc. 1977, sect. 1, vol. 1, pt. 1, chapt. 13, 99–136.
 73. Hirst, G. D. S. Neuromuscular transmission in arterioles of guinea‐pig submucosa. J. Physiol. Lond. 273: 87–104, 1977.
 74. Hirst, G. D. S. Identification of transmitters in the autonomic nervous system. Proc. Aust. Physiol. Pharmacol. Soc. 9: 91–93, 1978.
 75. Hirst, G. D. S., S. De Glaria, and D. F. van Helden. Neuromuscular transmission in arterioles. Experientia Basel 41: 874–879, 1985.
 76. Hirst, G. D. S., and M. J. Lew. Lack of involvement of alpha‐adrenoceptors in sympathetic neural vasoconstriction in the hindquarters of the rabbit. Brit. J. Pharmacol. 90: 51–60, 1987.
 77. Hirst, G. D. S., and E. M. McLachlan. Post‐natal development of ganglia in the lower lumbar sympathetic chain of the rat. J. Physiol. Lond. 349: 119–134, 1984.
 78. Hirst, G. D. S., and T. O. Neild. An analysis of excitatory junctional potentials recorded arterioles. J. Physiol. Lond. 280: 87–104, 1978.
 79. Hirst, G. D. S., and T. O. Neild. Some properties of spontaneous excitatory junction potentials recorded from arterioles of guinea‐pigs. J. Physiol. Lond. 303: 43–60, 1980.
 80. Hirst, G. D. S., and T. O. Neild. Evidence for two populations of excitatory receptors for noradrenaline on arteriolar smooth muscle. Nature Lond. 283: 767–768, 1980.
 81. Hirst, G. D. S., and T. O. Neild. Localization of specialized noradrenaline receptors at neuromuscular junctions on arterioles of the guinea‐pig. J. Physiol. Lond. 313: 343–350, 1981.
 82. Hirst, G. D. S., T. O. Neild, and G. D. Silverberg. Noradrenaline receptors on the rat basilar artery. J. Physiol. Lond. 328: 351–360, 1982.
 83. Hirst, G. D. S., G. D. Silverberg, and D. F. van Helden. The action potential and underlying ionic currents in proximal rat middle cerebral arterioles. J. Physiol. Lond. 371: 289–304, 1986.
 84. Hirst, G. D. S., and D. F. van Helden. Ionic basis of the resting potential of submucosal arterioles in the ileum of the guinea‐pig. J. Physiol. Lond. 333: 53–67, 1982.
 85. Hodgkin, A. L., and B. Katz. The effect of sodium ions on the electrical activity of the giant axon of the squid. J. Physiol. Lond. 148: 37–77, 1949.
 86. Hodgkin, A. L., and W. A. H. Rushton. The electrical constants of a crustacean nerve fibre. Proc. R. Soc. Lond. B Biol. Sci. 133: 444–479, 1946.
 87. Hökfelt, T. Distribution of noradrenaline storing particles in peripheral neurons as revealed by electron microscopy. Acta Physiol. Scand. 76: 427–440, 1969.
 88. Holman, M. E., C. B. Kasby, M. B. Suthers, and J. A. F. Wilson. Some properties of the smooth muscle of rabbit portal vein. J. Physiol. Lond. 196: 111–132, 1968.
 89. Holman, M. E., and A. M. Surprenant. Some properties of the excitatory junction potentials recorded from saphenous arteries of rabbits. J. Physiol. Lond. 287: 337–351, 1979.
 90. Holman, M. E., and A. M. Surprenant. Effects of tetraethylammonium chloride on sympathetic neuromuscular transmission in saphenous artery of young rabbits. J. Physiol. Lond. 305: 451–465, 1980.
 91. Holman, M. E., and A. M. Surprenant. An electrophysiological analysis of the effects of noradrenaline and receptor antagonists on neuromuscular transmission in mammalian muscular arteries. Br. J. Pharmacol. 71: 337–351, 1980.
 92. Hua, C., and B. Cragg. Measurements of smooth muscle cells in arterioles of guinea‐pig ileum. Acta Anat. 107: 224–230, 1980.
 93. Ishikawa, S. Actions of ATP and α,β‐methylene ATP on neuromuscular transmission and smooth muscle membranes of the rabbit and guinea‐pig mesenteric arteries. Br. J. Pharmacol. 86: 777–787, 1985.
 94. Itoh, T., K. Kitamura, and H. Kuriyama. Roles of extra‐junctional receptors in the response of guinea‐pig mesenteric and rat tail arteries to adrenergic nerves. J. Physiol. Lond. 345: 409–422, 1983.
 95. Iversen, L. L. The Uptake and Storage of Noradrenaline in Sympathetic Nerves. London: Cambridge Univ. Press, 1967.
 96. Jack, J. J. B., D. Noble, and R. W. Tsien. Electrical Current Flow in Excitable Cells. Oxford, UK: Clarendon, 1975.
 97. Jack, J. J. B., S. J. Redman, and K. Wong. The components of synaptic potentials evoked in cat spinal motoneurons by impulses in single 1a afferents. J. Physiol. Lond. 321: 65–96, 1981.
 98. Janig, W. Organization of the lumbar sympathetic outflow to skeletal muscle and skin of the cat hind limb and tail. Rev. Physiol. Biochem. Pharmacol. 102: 121–213, 1985.
 99. Kajiwara, M., K. Kitamura, and H. Kuriyama. Neuromuscular transmission and smooth muscle membrane properties in the guinea‐pig ear artery. J. Physiol. Lond. 315: 283–302, 1981.
 100. Kanmura, Y., T. Itoh, H. Suzuki, Y. Ito, and H. Kuriyama. Effects of nifedipine on smooth muscle cells of the rabbit mesenteric artery. J. Pharmacol. Exp. Ther. 226: 238–248, 1983.
 101. Katz, B. The Release of Neural Transmitter Substances. The Sherrington Lectures X, Liverpool, UK: Liverpool University, 1969.
 102. Keatinge, W. R. Ionic requirements for arterial action potential. J. Physiol. Lond. 194: 168–182, 1968.
 103. Keatinge, W. R. Mechanism of slow discharge of sheep carotid artery. J. Physiol. Lond. 279: 275–289, 1978.
 104. Kou, K., J. Ibenge, and H. Suzuki. Effects of alpha‐adrenoceptor antagonists on electrical and mechanical responses of the isolated dog mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline. Naunyn‐Schmiedeberg's Arch. Pharmacol. 326: 7–13, 1984.
 105. Kuffler, S. W., and J. G. Nicholls. From Neuron to Brain. Sunderland, MA: Sinauer, 1976.
 106. Kugelgen, I. V., and K. Starke. Noradrenaline and adenosine triphosphate as co‐transmitters of neurogenic vasoconstriction in rabbit mesenteric arteries. J. Physiol. Lond. 367: 435–455, 1985.
 107. Kuriyama, H. Electrophysiological observations on the motor innervation of the smooth muscle cells of the guinea‐pig vas deferens. J. Physiol. Lond. 169: 213–228, 1963.
 108. Kuriyama, H., and Y. Makita. Modulation of noradrenergic transmission in the guinea‐pig mesenteric artery: an electrophysiological study. J. Physiol. Lond. 335: 609–627, 1983.
 109. Kuriyama, H., and A. Suyama. Multiple actions of cocaine on neuromuscular transmission and smooth muscle cells of the guinea‐pig mesenteric artery. J. Physiol. Lond. 337: 631–654, 1983.
 110. Kuriyama, H., and H. Suzuki. Adrenergic transmission in the mesenteric artery and their cholinergic modulations. J. Physiol. Lond. 317: 383–396, 1981.
 111. Lagerecrantz, H. On the consumption and function of large dense cored vesicles in sympathetic nerves. Neuroscience 1: 81–92, 1976.
 112. Landis, S. C., and D. Keefe. Evidence for neurotransmitter plasticity in vivo: developmental changes in properties of cholinergic sympathetic neurones. Dev. Biol. 98: 349–372, 1983.
 113. Langer, S. Z. Presynaptic receptors and their role in regulation of transmitter release. Br. J. Pharmacol. 60: 481–497, 1977.
 114. Large, W. A. Membrane potential responses of the mouse. anococcygeus muscle to ionophoretically applied noradrenaline. J. Physiol. Lond. 326: 385–400, 1982.
 115. Large, W. A. Membrane potential responses to ionophoretically applied adrenoceptor agonists in the mouse anococcygeus muscle. Br. J. Pharmacol. 79: 233–243, 1983.
 116. Large, W. A. The effect of chloride removal on the responses of the isolated rat anococcygeus muscle to α1‐adrenoceptor stimulation. J. Physiol. Lond. 352: 17–29, 1984.
 117. Luff, S. E., E. M. McLachlan, and G. D. S. Hirst. An ultrastructural analysis of the sympathetic neuromuscular junctions on arterioles of the submucosa of the guinea pig ileum. J. Comp. Neurol. 257: 578–594, 1987.
 118. Martin, A. R. Quantal nature of synaptic transmission. Physiol. Rev. 46: 51–66, 1966.
 119. McGrath, J. C. Adrenergic and ‘non‐adrenergic’ components in the contractile response of the vas deferens to a single indirect stimulus. J. Physiol. Lond. 283: 23–39, 1978.
 120. McLachlan, E. M. The statistics of transmitter release at chemical synapses. In: Neurophysiology III, edited by R. Porter Baltimore, MD: University Park, 1978, vol. 17, p. 49–117. (Int. Rev. Physiol. Ser.).
 121. McLachlan, E. M., and G. D. S. Hirst. Some properties of preganglionic neurons in upper thoracic spinal cord of the cat. J. Neurophysiol. 43: 1251–1265, 1980.
 122. Mekata, F. Current‐spread in the smooth muscle of the rabbit aorta. J. Physiol. Lond. 242: 143–155, 1974.
 123. Mekata, F. Rectification in the smooth muscle cell membrane of rabbit aorta. J. Physiol. Lond. 258: 269–278, 1976.
 124. Melchiorre, C., M. S. Yong, B. G. Benfey, and B. Belleau. Molecular properties of the adrenergic α‐receptor. 2. Optimal covalent inhibition by two different prototypes of polyamine disulphides. J. Med. Chem. 21: 1126–1128, 1978.
 125. Morgan, K. G. Comparison of membrane electrical activity of cat gastric submucosal arterioles and venules. J. Physiol. Lond. 345: 135–147, 1983.
 126. Mulvany, M. J., H. Nilsson, and J. A. Flatman. Role of membrane potential in the response of rat small mesenteric arteries to exogenous noradrenaline stimulation. J. Physiol. Lond. 332: 539–551, 1982.
 127. Murumatsu, I., M. Fujiwara, A. Miura, and Y. Sakakibara. Possible involvement of adenine nucleotides in sympathetic neuroeffector mechanisms of dog basilar artery. J. Pharmacol. Exp. Ther. 216: 401–409, 1981.
 128. Murumatsu, I., S. Kigoshi, and M. Oshita. Nonadrenergic nature of prazosin‐resistant sympathetic contraction in the dog mesenteric artery. J. Pharmacol. Exp. Ther. 229: 532–538, 1984.
 129. Nakanishi, H., and H. Takeda. The possible role of adenosine triphosphate in chemical transmission between the hypogastric nerve terminal and seminal vesicle. Jpn. J. Pharmacol. 23: 479–483, 1973.
 130. Neild, T. O. The relation between the structure and innervation of small arteries and arterioles and the smooth muscle membrane potential changes expected at different levels of sympathetic nerve activity. Proc. R. Soc. Lond. B Biol. Sci.: 237–249, 1983.
 131. Neild, T. O. & E. Zelcer. Noradrenergic neuromuscular transmission with special reference to arterial smooth muscle. Prog. Neurobiol. 19: 141–158, 1982.
 132. Norberg, K. A., and B. Hamberger. The sympathetic adrenergic neuron. Some characteristics revealed by histochemical studies on the intraneuronal distribution of the transmitter. Acta Physiol. Scand. Suppl. 238: 1–42, 1964.
 133. O'Brien, R. A., M. Da Prada, and A. Pletscher. The ontogenesis of catecholamines and adenosine‐5'‐triphosphate in the adrenal medulla. Life Sci. 11: 749–759, 1972.
 134. Ohashi, H. An estimate of the proportion of the resting membrane conductance of the smooth muscle of taenia coli to chloride. J. Physiol. Lond. 210: 405–419, 1970.
 135. Rang, H. P. The characteristics of synaptic current and responses to acetylcholine of rat submandibular ganglion cells. J. Physiol. Lond. 311: 23–55, 1981.
 136. Redman, S. J. Synaptic transmission in the central nervous system. Prog. Neurobiol. 12: 33–83, 1979.
 137. Rhodin, J. A. G. The ultrastructure of mammalian arterioles and precapillary sphincters. J. Ultrastruct. Res. 18: 181–223, 1967.
 138. Rowan, R. A., and J. A. Bevan. Distribution of adrenergic synaptic cleft width in vascular and nonvascular smooth muscle. In: Vascular Neuroeffector Mechanisms, edited by J. A. Bevan New York: Raven, 1983, p. 75–83. (4th Int. Symp.).
 139. Shepherd, A. P., and D. N. Granger. Physiology of the Intestinal Circulation. New York: Raven, 1984.
 140. Skok, V. I. Physiology of Autonomic Ganglia. Tokyo: Igaku Shoin, 1975.
 141. Sneddon, P., and G. Burnstock. ATP as a co‐transmitter in rat tail artery. Eur. J. Pharmacol. 106: 149–152, 1984.
 142. Sneddon, P., and D. P. Westfall. Pharmacological evidence that adenosine triphosphate and noradrenaline are cotransmitters in the guinea‐pig vas deferens. J. Physiol. Lond. 347: 561–580, 1984.
 143. Sneddon, P., D. P. Westfall, and J. S. Fedan. Cotransmitters in the motor nerves of the guinea‐pig vas deferens: electrophysiological evidence. Science Wash. DC 218: 693–694, 1982.
 144. Somlyo, A. P., and A. V. Somlyo. Vascular smooth muscle. 1. Normal structure, pathology, biochemistry and biophysics. Pharmacol. Rev. 20: 197–272, 1968.
 145. Speden, R. N. Electrical activity of single smooth muscle cells of the mesenteric artery produced by splanchnic nerve stimulation in the guinea‐pig. Nature Lond. 202: 193–194, 1964.
 146. Speden, R. N. Excitation of vascular smooth muscle. In: Smooth Muscle, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1970, p. 558–588.
 147. Starke, K. Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77: 1–124, 1977.
 148. Steedman, W. A. Micro‐electrode studies on mammalian vascular muscle. J. Physiol. Lond. 186: 382–400, 1966.
 149. Stjärne, L., and P. Astrand. Relative pre‐ and postjunctional roles of noradrenaline and adenosine‐5'‐triphosphate as neurotransmitters of the sympathetic nerves of guinea‐pig vas deferens. Neuroscience 14: 929–946, 1985.
 150. Su, C. Neurogenic release of purine compounds in blood vessels. J. Pharmacol. Exp. Ther. 195: 159–166, 1975.
 151. Su, C., J. A. Bevan, and R. C. Ursillo. Electrical quiescence of pulmonary artery smooth muscle during sympathomimetic stimulation. Circ. Res. 15: 20–27, 1964.
 152. Suprenant, A. A comparative study of neuromuscular transmission in several mammalian muscular arteries. Pfluegers Arch. 396: 85–91, 1980.
 153. Suzuki, H. Effects of endogenous and exogenous noradrenaline on the smooth muscle of guinea‐pig mesenteric vein. J. Physiol. Lond. 321: 495–512, 1981.
 154. Suzuki, H. An electrophysiological study of excitatory neuromuscular transmission in the guinea‐pig main pulmonary artery. J. Physiol. Lond. 336: 47–59, 1983.
 155. Suzuki, H. Electrical responses of smooth muscle cells of the rabbit ear artery to adenosine triphosphate. J. Physiol. Lond. 359: 401–416, 1985.
 156. Suzuki, H., and K. Kou. Electrical components contributing to the nerve‐mediated contractions in the smooth muscles of the rabbit ear artery. Jpn. J. Physiol. 33: 743–756, 1983.
 157. Swedin, G. Biphasic mechanical response of the isolated vas deferens to nerve stimulation. Acta Physiol. Scand. 81: 574–576, 1971.
 158. Thomas, R. C. Electrogenic sodium pump in nerve and muscle cells. Physiol. Rev. 52: 563–594, 1972.
 159. Tomita, T. Electrical properties of mammalian smooth muscle. In: Smooth Muscle, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1970, p. 197–243.
 160. Tomita, T. Electrical activity (spikes and slow waves) in gastro‐intestinal smooth muscle. In: Smooth Muscle: an Assessment of Current Knowledge, edited by E. Bülbring, A. F. Brading, A. W. Jones, and T. Tomita. London: Arnold, 1981, p. 127–156.
 161. Vatner, S. F., D. R. Knight, and T. H. Hintze. Norepinephrine‐induced beta‐1 adrenergic peripheral vasodilation in conscious dogs. Am. J. Physiol. 249: 49–56, 1985.
 162. Westfall, D. P., R. E. Stitzel, and J. N. Rowe. The post‐junctional effects and neural release of purine compounds in the guinea‐pig vas deferens. Eur. J. Pharmacol. 50: 27–38, 1978.
 163. White, T., P. Potter, C. Moody, and G. Burnstock. Tetrodoxin resistant release of ATP from guinea‐pig taenia coli and vas deferens during electrical field stimulation in the presence of luciferin‐luciferase. Can. J. Physiol. Pharmacol. 59: 1094–1100, 1981.

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Article Title: Neuromuscular transmission in intramural blood vessels
 

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G. D. S. Hirst. Neuromuscular transmission in intramural blood vessels. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 1635-1665. First published in print 1989. doi: 10.1002/cphy.cp060145