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Ion Channels in the Heart

Daniel C. Bartos, Eleonora Grandi, Crystal M. Ripplinger

10.1002/cphy.c140069

Source: Volume 5, Issue 3, July 2015

Published online: June 2015

Full Article on Wiley Online Library



ABSTRACT

Optimal cardiac function depends on proper timing of excitation and contraction in various regions of the heart, as well as on appropriate heart rate. This is accomplished via specialized electrical properties of various components of the system, including the sinoatrial node, atria, atrioventricular node, His‐Purkinje system, and ventricles. Here we review the major regionally determined electrical properties of these cardiac regions and present the available data regarding the molecular and ionic bases of regional cardiac function and dysfunction. Understanding these differences is of fundamental importance for the investigation of arrhythmia mechanisms and pharmacotherapy. © 2015 American Physiological Society. Compr Physiol 5:1423‐1464, 2015.

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Figure 1. Figure 1. Regional heterogeneity of the electrical properties of the heart. (A) Schematic of different regions of the human heart and the corresponding (B) AP waveforms (below is a representative lead I ECG). (C) Overview of review organization. (D) Ion channel and regulatory protein gene expression are compared between corresponding regions of the heart [modified from (178) with permission]. The genes listed are significantly more strongly expressed in the region listed relative to the reference region indicated. SVC, superior vena cava; SAN, sinoatrial node; RA, right atrium; LA, left atrium; IVC, interventricular septum; AVN, atrioventricular node; RV, right ventricle; LV, left ventricle.
Figure 2. Figure 2. SAN structure and function. (A) Schematic showing endocardial view of SAN area (location corresponds to box around SAN in Fig. 1A). Approximate area of functional conduction block is shown in gray. (B) Transmural view of SAN showing organization of central and peripherial SAN cells. Redrawn from (74) with permission. (C) Example APs and ionic currents from central and peripheral SAN cells. Redrawn from (375) with permission. (D) Ivabradine, an I f blocker, slows SAN beat rate via slowing the rate of diastolic depolarization [with permission from (85)]. (E) Slowing of SAN beat rate also occurs with ryanodine, a blocker of RyR Ca2+ release, demonstrating the importance of the Ca2+ clock in contributing to normal SAN pacemaking [with permission from (64)]. CT, crista terminalis; CTL, control; Endo, endocardium; Epi, epicardium; IVC, inferior vena cava; RA, right atrium; RYAN, ryanodine; SEP, interatrial septum; SVC, superior vena cava.
Figure 3. Figure 3. Atrial myocyte function and dysfunction. AP, CaT, and major underlying ionic currents simulated with computational models of human atrial sinus rhythm (black) and AF (red) myocytes. Modified, with permission, from (196).
Figure 4. Figure 4. Heterogeneity of atrial electrophysiology. Three different outward current patterns in human atrial myocytes confer distinct AP shape and properties [(redrawn from (541) with permission].
Figure 5. Figure 5. Ionic mechanisms of ectopic activity and reentry. Left: cellular mechanisms of early and delayed afterdepolarizations and cardiac cell automaticity. Right: mechanisms of reentry, redrawn with permission from (531).
Figure 6. Figure 6. AVN structure and function. (A) Schematic showing endocardial view of AVN area (location corresponds to box around AVN in Fig. 1A). Redrawn from (232) with permission. (B) Example AN‐like AP. (C) Example N‐like AP. (D) Example NH‐like AP. Panels B‐D redrawn with permission from (342). AN, atrio‐nodal; CFB, central fibrous body; CN, compact node; CS, coronary sinus; HIS, penetrating His bundle; IAS, interatrial septum; INE, inferior nodal extension; N, nodal; NH, nodal‐His; TT, tendon of Todaro; TV, tricuspid valve; TZ, transitional zone; VS, ventricular septum.
Figure 7. Figure 7. Ventricular AP and ion currents. Depicted in this figure are (A) simulated human ventricular AP (black) and CaT (blue). (B) The major depolarizing Na+ (I Na, red) and Ca2+ (I CaL, blue) currents (inset shows the different time‐course of activation and current decay), (C) the major repolarizing K+ currents (I to, purple; I Kr, brown; I Ks, black, and I K1, green), and (D) Na+/Ca2+ exchange (I NCX, turquoise) and Na+/K+ pump (I NKA, black) currents during a ventricular AP are shown (194). Redrawn, with permission, from (192).
Figure 8. Figure 8. Species Differences in ventricular AP waveforms and drug response. (A) Representative traces of ECG recordings from lead I of a human and mouse are depicted [redrawn, with permission, from (251)]. Inset shows a single P‐S interval of the mouse ECG. (B) A rabbit ventricular AP (i) is shortened and loses its plateau (ii‐v) as mouse K+ currents are integrated. (C) The simulated I‐V relations of mouse I to, I k,slow, I ss, and I K1 that are added to the rabbit AP simulation are plotted [reprinted, with permission, from (339)]. (D) Shown are ventricular AP recordings of I Kr or I Ks block in human, dog, or guinea pig. The figure demonstrates the species‐specific sensitivity to drug block and changes in AP morphology [reprinted, with permission, from (416)].
Figure 9. Figure 9. Multiple mechanisms underlie ventricular arrhythmia in HF. (A) Sustained focal ventricular tachycardia (VT) induced following local sympathetic stimulation in a normal rabbit heart pretreated with 50 μmol/L BaCl2 to reduce I K1 and 200 μmol/L caffeine to sensitize RyR. When applied simultaneously, a highly arrhythmogenic phenotype was observed, but neither condition alone (BaCl2 or caffeine) produced an increase in arrhythmic events (not shown). (B) Activation map demonstrating the focal origin and spread of propagation of a single beat of VT. (C) Superimposed E m (black) and [Ca2+]i (red) traces from the origin of focal activity showing diastolic E m and [Ca2+]i elevation [reprinted, with permission, from (343)].


Figure 1. Regional heterogeneity of the electrical properties of the heart. (A) Schematic of different regions of the human heart and the corresponding (B) AP waveforms (below is a representative lead I ECG). (C) Overview of review organization. (D) Ion channel and regulatory protein gene expression are compared between corresponding regions of the heart [modified from (178) with permission]. The genes listed are significantly more strongly expressed in the region listed relative to the reference region indicated. SVC, superior vena cava; SAN, sinoatrial node; RA, right atrium; LA, left atrium; IVC, interventricular septum; AVN, atrioventricular node; RV, right ventricle; LV, left ventricle.


Figure 2. SAN structure and function. (A) Schematic showing endocardial view of SAN area (location corresponds to box around SAN in Fig. 1A). Approximate area of functional conduction block is shown in gray. (B) Transmural view of SAN showing organization of central and peripherial SAN cells. Redrawn from (74) with permission. (C) Example APs and ionic currents from central and peripheral SAN cells. Redrawn from (375) with permission. (D) Ivabradine, an I f blocker, slows SAN beat rate via slowing the rate of diastolic depolarization [with permission from (85)]. (E) Slowing of SAN beat rate also occurs with ryanodine, a blocker of RyR Ca2+ release, demonstrating the importance of the Ca2+ clock in contributing to normal SAN pacemaking [with permission from (64)]. CT, crista terminalis; CTL, control; Endo, endocardium; Epi, epicardium; IVC, inferior vena cava; RA, right atrium; RYAN, ryanodine; SEP, interatrial septum; SVC, superior vena cava.


Figure 3. Atrial myocyte function and dysfunction. AP, CaT, and major underlying ionic currents simulated with computational models of human atrial sinus rhythm (black) and AF (red) myocytes. Modified, with permission, from (196).


Figure 4. Heterogeneity of atrial electrophysiology. Three different outward current patterns in human atrial myocytes confer distinct AP shape and properties [(redrawn from (541) with permission].


Figure 5. Ionic mechanisms of ectopic activity and reentry. Left: cellular mechanisms of early and delayed afterdepolarizations and cardiac cell automaticity. Right: mechanisms of reentry, redrawn with permission from (531).


Figure 6. AVN structure and function. (A) Schematic showing endocardial view of AVN area (location corresponds to box around AVN in Fig. 1A). Redrawn from (232) with permission. (B) Example AN‐like AP. (C) Example N‐like AP. (D) Example NH‐like AP. Panels B‐D redrawn with permission from (342). AN, atrio‐nodal; CFB, central fibrous body; CN, compact node; CS, coronary sinus; HIS, penetrating His bundle; IAS, interatrial septum; INE, inferior nodal extension; N, nodal; NH, nodal‐His; TT, tendon of Todaro; TV, tricuspid valve; TZ, transitional zone; VS, ventricular septum.


Figure 7. Ventricular AP and ion currents. Depicted in this figure are (A) simulated human ventricular AP (black) and CaT (blue). (B) The major depolarizing Na+ (I Na, red) and Ca2+ (I CaL, blue) currents (inset shows the different time‐course of activation and current decay), (C) the major repolarizing K+ currents (I to, purple; I Kr, brown; I Ks, black, and I K1, green), and (D) Na+/Ca2+ exchange (I NCX, turquoise) and Na+/K+ pump (I NKA, black) currents during a ventricular AP are shown (194). Redrawn, with permission, from (192).


Figure 8. Species Differences in ventricular AP waveforms and drug response. (A) Representative traces of ECG recordings from lead I of a human and mouse are depicted [redrawn, with permission, from (251)]. Inset shows a single P‐S interval of the mouse ECG. (B) A rabbit ventricular AP (i) is shortened and loses its plateau (ii‐v) as mouse K+ currents are integrated. (C) The simulated I‐V relations of mouse I to, I k,slow, I ss, and I K1 that are added to the rabbit AP simulation are plotted [reprinted, with permission, from (339)]. (D) Shown are ventricular AP recordings of I Kr or I Ks block in human, dog, or guinea pig. The figure demonstrates the species‐specific sensitivity to drug block and changes in AP morphology [reprinted, with permission, from (416)].


Figure 9. Multiple mechanisms underlie ventricular arrhythmia in HF. (A) Sustained focal ventricular tachycardia (VT) induced following local sympathetic stimulation in a normal rabbit heart pretreated with 50 μmol/L BaCl2 to reduce I K1 and 200 μmol/L caffeine to sensitize RyR. When applied simultaneously, a highly arrhythmogenic phenotype was observed, but neither condition alone (BaCl2 or caffeine) produced an increase in arrhythmic events (not shown). (B) Activation map demonstrating the focal origin and spread of propagation of a single beat of VT. (C) Superimposed E m (black) and [Ca2+]i (red) traces from the origin of focal activity showing diastolic E m and [Ca2+]i elevation [reprinted, with permission, from (343)].
References
 1. Abbott GW , Sesti F , Splawski I , Buck ME , Lehmann MH , Timothy KW , Keating MT , Goldstein SA . MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97: 175‐187, 1999.
 2. Ai X , Curran JW , Shannon TR , Bers DM , Pogwizd SM . Ca2+/calmodulin‐dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure. Circ Res 97: 1314‐1322, 2005.
 3. Aiba T , Tomaselli GF . Electrical remodeling in the failing heart. Curr Opin Cardiol 25: 29‐36, 2010.
 4. Akar FG , Rosenbaum DS . Transmural electrophysiological heterogeneities underlying arrhythmogenesis in heart failure. Circ Res 93: 638‐645, 2003.
 5. Akar FG , Wu RC , Juang GJ , Tian Y , Burysek M , Disilvestre D , Xiong W , Armoundas AA , Tomaselli GF . Molecular mechanisms underlying K+ current downregulation in canine tachycardia‐induced heart failure. Am J Physiol Heart Circ Physiol 288: H2887‐H2896, 2005.
 6. Alings AM , Abbas RF , Bouman LN . Age‐related changes in structure and relative collagen content of the human and feline sinoatrial node. A comparative study. Eur Heart J 16: 1655‐1667, 1995.
 7. Alings AM , Bouman LN . Electrophysiology of the ageing rabbit and cat sinoatrial node—A comparative study. Eur Heart J 14: 1278‐1288, 1993.
 8. Amos GJ , Wettwer E , Metzger F , Li Q , Himmel HM , Ravens U . Differences between outward currents of human atrial and subepicardial ventricular myocytes. J Physiol 491(Pt 1): 31‐50, 1996.
 9. An WF , Bowlby MR , Betty M , Cao J , Ling HP , Mendoza G , Hinson JW , Mattsson KI , Strassle BW , Trimmer JS , Rhodes KJ . Modulation of A‐type potassium channels by a family of calcium sensors. Nature 403: 553‐556, 2000.
 10. Andelfinger G , Tapper AR , Welch RC , Vanoye CG , George AL , Benson DW . KCNJ2 mutation results in Andersen syndrome with sex‐specific cardiac and skeletal muscle phenotypes. Am J Hum Gen 71: 663‐668, 2002.
 11. Anderson ME , Brown JH , Bers DM . CaMKII in myocardial hypertrophy and heart failure. J Mol Cell Cardiol 51: 468‐473, 2011.
 12. Ansari A , Ho SY , Anderson RH . Distribution of the Purkinje fibres in the sheep heart. Anat Rec 254: 92‐97, 1999.
 13. Anter E , Jessup M , Callans DJ . Atrial fibrillation and heart failure: Treatment considerations for a dual epidemic. Circulation 119: 2516‐2525, 2009.
 14. Antzelevitch C . The M Cell. J Cardiovasc Pharmacol Ther 2: 73‐76, 1997.
 15. Antzelevitch C . Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. Am J Physiol Heart Circ Physiol 293: H2024‐H2038, 2007.
 16. Antzelevitch C . Drug‐induced spatial dispersion of repolarization. Cardiol J 15: 100‐121, 2008.
 17. Antzelevitch C , Brugada P , Brugada J , Brugada R . Brugada syndrome: From cell to bedside. Curr Probl Cardiol 30: 9‐54, 2005.
 18. Antzelevitch C , Pollevick GD , Cordeiro JM , Casis O , Sanguinetti MC , Aizawa Y , Guerchicoff A , Pfeiffer R , Oliva A , Wollnik B , Gelber P , Bonaros EP, Jr. , Burashnikov E , Wu Y , Sargent JD , Schickel S , Oberheiden R , Bhatia A , Hsu LF , Haissaguerre M , Schimpf R , Borggrefe M , Wolpert C . Loss‐of‐function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST‐segment elevation, short QT intervals, and sudden cardiac death. Circulation 115: 442‐449, 2007.
 19. Antzelevitch C , Sicouri S , Litovsky SH , Lukas A , Krishnan SC , Di Diego JM , Gintant GA , Liu DW . Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ Res 69: 1427‐1449, 1991.
 20. Anumonwo JM , Tallini YN , Vetter FJ , Jalife J . Action potential characteristics and arrhythmogenic properties of the cardiac conduction system of the murine heart. Circ Res 89: 329‐335, 2001.
 21. Apkon M , Nerbonne JM . Characterization of two distinct depolarization‐activated K+ currents in isolated adult rat ventricular myocytes. J Gen Physiol 97: 973‐1011, 1991.
 22. Arikkath J , Campbell KP . Auxiliary subunits: Essential components of the voltage‐gated calcium channel complex. Curr Opin Neurobiol 13: 298‐307, 2003.
 23. Armoundas AA , Hobai IA , Tomaselli GF , Winslow RL , O'Rourke B . Role of sodium‐calcium exchanger in modulating the action potential of ventricular myocytes from normal and failing hearts. Circ Res 93: 46‐53, 2003.
 24. Aslanidi OV , Sleiman RN , Boyett MR , Hancox JC , Zhang H . Ionic mechanisms for electrical heterogeneity between rabbit Purkinje fiber and ventricular cells. Biophys J 98: 2420‐2431, 2010.
 25. Atkinson A , Inada S , Li J , Tellez JO , Yanni J , Sleiman R , Allah EA , Anderson RH , Zhang H , Boyett MR , Dobrzynski H . Anatomical and molecular mapping of the left and right ventricular His‐Purkinje conduction networks. J Mol Cell Cardiol 51: 689‐701, 2011.
 26. Atkinson AJ , Logantha SJRJ , Hao G , Yanni J , Fedorenko O , Sinha A , Gilbert SH , Benson AP , Buckley DL , Anderson RH , Boyett MR , Dobrzynski H . Functional, anatomical, and molecular investigation of the cardiac conduction system and arrhythmogenic atrioventricular ring tissue in the rat heart. J Am Heart Assoc 2: e000246, 2013.
 27. Balana B , Dobrev D , Wettwer E , Christ T , Knaut M , Ravens U . Decreased ATP‐sensitive K(+) current density during chronic human atrial fibrillation. J Mol Cell Cardiol 35: 1399‐1405, 2003.
 28. Balasundaram R , Rao HB , Kalavakolanu S , Narasimhan C . Catheter ablation of bundle branch reentrant ventricular tachycardia. Heart Rhythm 5: S68‐S72, 2008.
 29. Banyasz T , Fulop L , Magyar J , Szentandrassy N , Varro A , Nanasi PP . Endocardial versus epicardial differences in L‐type calcium current in canine ventricular myocytes studied by action potential voltage clamp. Cardiovasc Res 58: 66‐75, 2003.
 30. Barhanin J , Lesage F , Guillemare E , Fink M , Lazdunski M , Romey G . K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current. Nature 384: 78‐80, 1996.
 31. Barry DM , Xu H , Schuessler RB , Nerbonne JM . Functional knockout of the transient outward current, long‐QT syndrome, and cardiac remodeling in mice expressing a dominant‐negative Kv4 alpha subunit. Circ Res 83: 560‐567, 1998.
 32. Bartos DC , Anderson JB , Bastiaenen R , Johnson JN , Gollob MH , Tester DJ , Burgess DE , Homfray T , Behr ER , Ackerman MJ , Guicheney P , Delisle BP . A KCNQ1 mutation causes a high penetrance for familial atrial fibrillation. J Cardiovasc Electrophysiol 24: 562‐569, 2013.
 33. Bartos DC , Duchatelet S , Burgess DE , Klug D , Denjoy I , Peat R , Lupoglazoff JM , Fressart V , Berthet M , Ackerman MJ , January CT , Guicheney P , Delisle BP . R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation. Heart Rhythm 8: 48‐55, 2011.
 34. Bartos DC , Giudicessi JR , Tester DJ , Ackerman MJ , Ohno S , Horie M , Gollob MH , Burgess DE , Delisle BP . A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation. Heart Rhythm 11: 459‐468, 2014.
 35. Baruscotti M , Bucchi A , Viscomi C , Mandelli G , Consalez G , Gnecchi‐Rusconi T , Montano N , Casali KR , Micheloni S , Barbuti A , DiFrancesco D . Deep bradycardia and heart block caused by inducible cardiac‐specific knockout of the pacemaker channel gene Hcn4. Proc Natl Acad Sci U S A 108: 1705‐1710, 2011.
 36. Bassani RA . Transient outward potassium current and Ca2+ homeostasis in the heart: Beyond the action potential. Braz J Med Biol Res 39: 393‐403, 2006.
 37. Bean BP . Two kinds of calcium channels in canine atrial cells. Differences in kinetics, selectivity, and pharmacology. J Gen Physiol 86: 1‐30, 1985.
 38. Bellocq C , van Ginneken AC , Bezzina CR , Alders M , Escande D , Mannens MM , Baro I , Wilde AA . Mutation in the KCNQ1 gene leading to the short QT‐interval syndrome. Circulation 109: 2394‐2397, 2004.
 39. Belus A , Piroddi N , Ferrantini C , Tesi C , Cazorla O , Toniolo L , Drost M , Mearini G , Carrier L , Rossi A , Mugelli A , Cerbai E , van der Velden J , Poggesi C . Effects of chronic atrial fibrillation on active and passive force generation in human atrial myofibrils. Circ Res 107: 144‐152, 2010.
 40. Ben Caref E , Boutjdir M , Himel HD , El‐Sherif N . Role of subendocardial Purkinje network in triggering torsade de pointes arrhythmia in experimental long QT syndrome. Europace 10: 1218‐1223, 2008.
 41. Bendahhou S , Marionneau C , Haurogne K , Larroque MM , Derand R , Szuts V , Escande D , Demolombe S , Barhanin J . In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart. Cardiovasc Res 67: 529‐538, 2005.
 42. Benito B , Brugada R , Perich RM , Lizotte E , Cinca J , Mont L , Berruezo A , Tolosana JM , Freixa X , Brugada P , Brugada J . A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation. Heart Rhythm 5: 1434‐1440, 2008.
 43. Benndorf K , Nilius B . Properties of an early outward current in single cells of the mouse ventricle. Gen Physiol Biophys 7: 449‐466, 1988.
 44. Bennett PB , Yazawa K , Makita N , George AL, Jr . Molecular mechanism for an inherited cardiac arrhythmia. Nature 376: 683‐685, 1995.
 45. Benson DW , Wang DW , Dyment M , Knilans TK , Fish FA , Strieper MJ , Rhodes TH , George AL . Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest 112: 1019‐1028, 2003.
 46. Bers DM. Excitation‐Contraction Coupling and Cardiac Contractile Force. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2001.
 47. Bers DM . Cardiac excitation‐contraction coupling. Nature 415: 198‐205, 2002.
 48. Bers DM . Ryanodine receptor S2808 phosphorylation in heart failure: Smoking gun or red herring. Circ Res 110: 796‐799, 2012.
 49. Bers DM . Cardiac sarcoplasmic reticulum calcium leak: Basis and roles in cardiac dysfunction. Annu Rev Physiol 76: 107‐127, 2014.
 50. Bers DM , Eisner DA , Valdivia HH . Sarcoplasmic reticulum Ca2+ and heart failure: Roles of diastolic leak and Ca2+ transport. Circ Res 93: 487‐490, 2003.
 51. Bers DM , Pogwizd SM , Schlotthauer K . Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure. Basic Res Cardiol 97 (Suppl 1): I36‐42, 2002.
 52. Bertaso F , Sharpe CC , Hendry BM , James AF . Expression of voltage‐gated K+ channels in human atrium. Basic Res Cardiol 97: 424‐433, 2002.
 53. Bettoni M , Zimmermann M . Autonomic tone variations before the onset of paroxysmal atrial fibrillation. Circulation 105: 2753‐2759, 2002.
 54. Beuckelmann DJ , Nabauer M , Erdmann E . Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure. Circ Res 73: 379‐385, 1993.
 55. Beyer EC , Paul DL , Goodenough DA . Connexin family of gap junction proteins. J Membr Biol 116: 187‐194, 1990.
 56. Bezzina CR , Rook MB , Groenewegen WA , Herfst LJ , van der Wal AC , Lam J , Jongsma HJ , Wilde AAM , Mannens MMAM . Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system. Circ Res 92: 159‐168, 2003.
 57. Bhuiyan ZA , van den Berg MP , van Tintelen JP , Bink‐Boelkens MTE , Wiesfeld ACP , Alders M , Postma AV , van Langen I , Mannens MMAM , Wilde AAM . Expanding spectrum of human RYR2‐related disease: New electrocardiographic, structural, and genetic features. Circulation 116: 1569‐1576, 2007.
 58. Billette J . Atrioventricular nodal activation during periodic premature stimulation of the atrium. Am J PhysiolAm J Physiol 252: H163‐H177, 1987.
 59. Blechschmidt S , Haufe V , Benndorf K , Zimmer T . Voltage‐gated Na+ channel transcript patterns in the mammalian heart are species‐dependent. Prog Biophys Mol Biol 98: 309‐318, 2008.
 60. Bleeker WK , Mackaay AJ , Masson‐Pévet M , Bouman LN , Becker AE . Functional and morphological organization of the rabbit sinus node. Circ Res 46: 11‐22, 1980.
 61. Bogdanov KY , Maltsev VA , Vinogradova TM , Lyashkov AE , Spurgeon HA , Stern MD , Lakatta EG . Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state. Circ Res 99: 979‐987, 2006.
 62. Bogdanov KY , Vinogradova TM , Lakatta EG . Sinoatrial nodal cell ryanodine receptor and Na(+)‐Ca(2+) exchanger: Molecular partners in pacemaker regulation. Circ Res 88: 1254‐1258, 2001.
 63. Bois P , Bescond J , Renaudon B , Lenfant J . Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol 118: 1051‐1057, 1996.
 64. Boogers MJ , Borleffs CJ , Henneman MM , van Bommel RJ , van Ramshorst J , Boersma E , Dibbets‐Schneider P , Stokkel MP , van der Wall EE , Schalij MJ , Bax JJ . Cardiac sympathetic denervation assessed with 123‐iodine metaiodobenzylguanidine imaging predicts ventricular arrhythmias in implantable cardioverter‐defibrillator patients. J Am Coll Cardiol 55: 2769‐2777, 2010.
 65. Borlak J , Thum T . Hallmarks of ion channel gene expression in end‐stage heart failure. FASEB J 17: 1592‐1608, 2003.
 66. Bosch RF , Gaspo R , Busch AE , Lang HJ , Li GR , Nattel S . Effects of the chromanol 293B, a selective blocker of the slow, component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes. Cardiovasc Res 38: 441‐450, 1998.
 67. Bosch RF , Zeng X , Grammer JB , Popovic K , Mewis C , Kuhlkamp V . Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 44: 121‐131, 1999.
 68. Boukens BJ , Christoffels VM , Coronel R , Moorman AF . Developmental basis for electrophysiological heterogeneity in the ventricular and outflow tract myocardium as a substrate for life‐threatening ventricular arrhythmias. Circ Res 104: 19‐31, 2009.
 69. Boyden PA , Barbhaiya C , Lee T , Ter Keurs HEDJ . Nonuniform Ca2+ transients in arrhythmogenic Purkinje cells that survive in the infarcted canine heart. Cardiovasc Res 57: 681‐693, 2003.
 70. Boyden PA , Dun W , Barbhaiya C , Ter Keurs HEDJ . 2APB‐ and JTV519(K201)‐sensitive micro Ca2+ waves in arrhythmogenic Purkinje cells that survive in infarcted canine heart. Heart Rhythm 1: 218‐226, 2004.
 71. Boyden PA , Pu J , Pinto J , Keurs HE . Ca(2+) transients and Ca(2+) waves in purkinje cells : role in action potential initiation. Circ Res 86: 448‐455, 2000.
 72. Boyett MR , Dobrzynski H , Lancaster MK , Jones SA , Honjo H , Kodama I . Sophisticated architecture is required for the sinoatrial node to perform its normal pacemaker function. J Cardiovasc Electrophysiol 14: 104‐106, 2003.
 73. Boyett MR , Hart G , Levi AJ , Roberts A . Effects of repetitive activity on developed force and intracellular sodium in isolated sheep and dog Purkinje fibres. J Physiol 388: 295‐322, 1987.
 74. Boyett MR , Honjo H , Kodama I . The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res 47: 658‐687, 2000.
 75. Bozler E . The initiation of impulses in cardiac muscle. Am J Physiol 138: 273‐282, 1943.
 76. Brahmajothi MV , Morales MJ , Reimer KA , Strauss HC . Regional localization of ERG, the channel protein responsible for the rapid component of the delayed rectifier, K+ current in the ferret heart. Circ Res 81: 128‐135, 1997.
 77. Brandt MC , Priebe L , Bohle T , Sudkamp M , Beuckelmann DJ . The ultrarapid and the transient outward K+ current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation. J Mol Cell Cardiol 32: 1885‐1896, 2000.
 78. Brette F , Orchard CH . Density and sub‐cellular distribution of cardiac and neuronal sodium channel isoforms in rat ventricular myocytes. Biochem Biophy Res Comm 348: 1163‐1166, 2006.
 79. Brugada R , Hong K , Dumaine R , Cordeiro J , Gaita F , Borggrefe M , Menendez TM , Brugada J , Pollevick GD , Wolpert C , Burashnikov E , Matsuo K , Wu YS , Guerchicoff A , Bianchi F , Giustetto C , Schimpf R , Brugada P , Antzelevitch C . Sudden death associated with short‐QT syndrome linked to mutations in HERG. Circulation 109: 30‐35, 2004.
 80. Brundel BJ , Van Gelder IC , Henning RH , Tieleman RG , Tuinenburg AE , Wietses M , Grandjean JG , Van Gilst WH , Crijns HJ . Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation. Circulation 103: 684‐690, 2001.
 81. Brundel BJ , van Gelder IC , Henning RH , Tuinenburg AE , Deelman LE , Tieleman RG , Grandjean JG , van Gilst WH , Crijns HJ . Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation. Cardiovasc Res 42: 443‐454, 1999.
 82. Brundel BJ , Van Gelder IC , Henning RH , Tuinenburg AE , Wietses M , Grandjean JG , Wilde AA , Van Gilst WH , Crijns HJ . Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: Differential regulation of protein and mRNA levels for K+ channels. J Am Coll Cardiol 37: 926‐932, 2001.
 83. Bucchi A , Barbuti A , Baruscotti M , DiFrancesco D . Heart rate reduction via selective ‘funny’ channel blockers. Curr Opin Pharmacol 7: 208‐213, 2007.
 84. Burashnikov A , Antzelevitch C . Prominent I(Ks) in epicardium and endocardium contributes to development of transmural dispersion of repolarization but protects against development of early afterdepolarizations. J Cardiovasc Electrophysiol 13: 172‐177, 2002.
 85. Burashnikov A , Antzelevitch C . Reinduction of atrial fibrillation immediately after termination of the arrhythmia is mediated by late phase 3 early afterdepolarization‐induced triggered activity. Circulation 107: 2355‐2360, 2003.
 86. Burashnikov A , Di Diego JM , Zygmunt AC , Belardinelli L , Antzelevitch C . Atrium‐selective sodium channel block as a strategy for suppression of atrial fibrillation: Differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation 116: 1449‐1457, 2007.
 87. Burashnikov A , Di Diego JM , Zygmunt AC , Belardinelli L , Antzelevitch C . Atrial‐selective sodium channel block as a strategy for suppression of atrial fibrillation. Ann N Y Acad Sci 1123: 105‐112, 2008.
 88. Burashnikov E , Pfeiffer R , Barajas‐Martinez H , Delpon E , Hu D , Desai M , Borggrefe M , Haissaguerre M , Kanter R , Pollevick GD , Guerchicoff A , Laino R , Marieb M , Nademanee K , Nam GB , Robles R , Schimpf R , Stapleton DD , Viskin S , Winters S , Wolpert C , Zimmern S , Veltmann C , Antzelevitch C . Mutations in the cardiac L‐type calcium channel associated with inherited J‐wave syndromes and sudden cardiac death. Heart Rhythm 7: 1872‐1882, 2010.
 89. Burgess DE , Crawford O , Delisle BP , Satin J . Mechanism of inactivation gating of human T‐type (low‐voltage activated) calcium channels. Biophys J 82: 1894‐1906, 2002.
 90. Burke MA , Mutharasan RK , Ardehali H . The sulfonylurea receptor, an atypical ATP‐binding cassette protein, and its regulation of the KATP channel. Circ Res 102: 164‐176, 2008.
 91. Butters TD , Aslanidi OV , Inada S , Boyett MR , Hancox JC , Lei M , Zhang H . Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome. Circ Res 107: 126‐137, 2010.
 92. Caballero R , de la Fuente MG , Gómez R , Barana A , Amorós I , Dolz‐Gaitón P , Osuna L , Almendral J , Atienza F , Fernández‐Avilés F , Pita A , Rodríguez‐Roda J , Pinto Á , Tamargo J , Delpón E . In humans, chronic atrial fibrillation decreases the transient outward current and ultrarapid component of the delayed rectifier current differentially on each atria and increases the slow component of the delayed rectifier current in both. J Am Coll Cardiol 55: 2346‐2354, 2010.
 93. Campuzano O , Brugada R . Genetics of familial atrial fibrillation. Europace 11: 1267‐1271, 2009.
 94. Cao JM , Fishbein MC , Han JB , Lai WW , Lai AC , Wu TJ , Czer L , Wolf PL , Denton TA , Shintaku IP , Chen PS , Chen LS . Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation 101: 1960‐1969, 2000.
 95. Carbone E , Lux HD . Kinetics and selectivity of a low‐voltage‐activated calcium current in chick and rat sensory neurones. J Physiol 386: 547‐570, 1987a.
 96. Carbone E , Lux HD . Single low‐voltage‐activated calcium channels in chick and rat sensory neurones. J Physiol 386: 571‐601, 1987b.
 97. Cerrone M , Noujaim SF , Tolkacheva EG , Talkachou A , O'Connell R , Berenfeld O , Anumonwo J , Pandit SV , Vikstrom K , Napolitano C , Priori SG , Jalife J . Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ Res 101: 1039‐1048, 2007.
 98. Chambers JC , Zhao J , Terracciano CM , Bezzina CR , Zhang W , Kaba R , Navaratnarajah M , Lotlikar A , Sehmi JS , Kooner MK , Deng G , Siedlecka U , Parasramka S , El‐Hamamsy I , Wass MN , Dekker LR , de Jong JS , Sternberg MJ , McKenna W , Severs NJ , de Silva R , Wilde AA , Anand P , Yacoub M , Scott J , Elliott P , Wood JN , Kooner JS . Genetic variation in SCN10A influences cardiac conduction. Nat Genet 42: 149‐152, 2010.
 99. Chandler NJ , Greener ID , Tellez JO , Inada S , Musa H , Molenaar P , DiFrancesco D , Baruscotti M , Longhi R , Anderson RH , Billeter R , Sharma V , Sigg DC , Boyett MR , Dobrzynski H . Molecular architecture of the human sinus node: Insights into the function of the cardiac pacemaker. Circulation 119: 1562‐1575, 2009.
 100. Chang PC , Turker I , Lopshire JC , Masroor S , Nguyen BL , Tao W , Rubart M , Chen PS , Chen Z , Ai T . Heterogeneous upregulation of apamin‐sensitive potassium currents in failing human ventricles. J Am Heart Assoc 2: e004713, 2013.
 101. Chelu MG , Sarma S , Sood S , Wang S , van Oort RJ , Skapura DG , Li N , Santonastasi M , Muller FU , Schmitz W , Schotten U , Anderson ME , Valderrabano M , Dobrev D , Wehrens XH . Calmodulin kinase II‐mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest 119: 1940‐1951, 2009.
 102. Chen L , Marquardt ML , Tester DJ , Sampson KJ , Ackerman MJ , Kass RS . Mutation of an A‐kinase‐anchoring protein causes long‐QT syndrome. Proc Natl Acad Sci U S A 104: 20990‐20995, 2007.
 103. Chen PS , Chen LS , Cao JM , Sharifi B , Karagueuzian HS , Fishbein MC . Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death. Cardiovasc Res 50: 409‐416, 2001.
 104. Chen PS , Chen LS , Fishbein MC , Lin SF , Nattel S . Role of the autonomic nervous system in atrial fibrillation: Pathophysiology and therapy. Circ Res 114: 1500‐1515, 2014.
 105. Chen Q , Kirsch GE , Zhang D , Brugada R , Brugada J , Brugada P , Potenza D , Moya A , Borggrefe M , Breithardt G , Ortiz‐Lopez R , Wang Z , Antzelevitch C , O'Brien RE , Schulze‐Bahr E , Keating MT , Towbin JA , Wang Q . Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 392: 293‐296, 1998.
 106. Chen X , Piacentino V, 3rd , Furukawa S , Goldman B , Margulies KB , Houser SR . L‐type Ca2+ channel density and regulation are altered in failing human ventricular myocytes and recover after support with mechanical assist devices. Circ Res 91: 517‐524, 2002.
 107. Chen YH , Xu SJ , Bendahhou S , Wang XL , Wang Y , Xu WY , Jin HW , Sun H , Su XY , Zhuang QN , Yang YQ , Li YB , Liu Y , Xu HJ , Li XF , Ma N , Mou CP , Chen Z , Barhanin J , Huang W . KCNQ1 gain‐of‐function mutation in familial atrial fibrillation. Science 299: 251‐254, 2003.
 108. Cheng EP , Yuan C , Navedo MF , Dixon RE , Nieves‐Cintron M , Scott JD , Santana LF . Restoration of normal L‐type Ca2+ channel function during Timothy syndrome by ablation of an anchoring protein. Circ Res 109: 255‐261, 2011.
 109. Cheng J , Kamiya K , Liu W , Tsuji Y , Toyama J , Kodama I . Heterogeneous distribution of the two components of delayed rectifier K+ current: A potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents. Cardiovasc Res 43: 135‐147, 1999.
 110. Christ T , Boknik P , Wohrl S , Wettwer E , Graf EM , Bosch RF , Knaut M , Schmitz W , Ravens U , Dobrev D . L‐Type Ca2+ current downregulation in chronic human atrial fibrillation is associated with increased activity of protein phosphatases. Circulation 110: 2651‐2657, 2004.
 111. Christ T , Wettwer E , Voigt N , Hala O , Radicke S , Matschke K , Varro A , Dobrev D , Ravens U . Pathology‐specific effects of the IKur/Ito/IK,ACh blocker AVE0118 on ion channels in human chronic atrial fibrillation. Br J Pharmacol 154: 1619‐1630, 2008.
 112. Christophersen IE , Olesen MS , Liang B , Andersen MN , Larsen AP , Nielsen JB , Haunso S , Olesen SP , Tveit A , Svendsen JH , Schmitt N . Genetic variation in KCNA5: Impact on the atrial‐specific potassium current IKur in patients with lone atrial fibrillation. Eur Heart J 34: 1517‐1525, 2013.
 113. Chua SK , Chang PC , Maruyama M , Turker I , Shinohara T , Shen MJ , Chen Z , Shen C , Rubart‐von der Lohe M , Lopshire JC , Ogawa M , Weiss JN , Lin SF , Ai T , Chen PS . Small‐conductance calcium‐activated potassium channel and recurrent ventricular fibrillation in failing rabbit ventricles. Circ Res 108: 971‐979, 2011.
 114. Clark RB , Bouchard RA , Salinas‐Stefanon E , Sanchez‐Chapula J , Giles WR . Heterogeneity of action potential waveforms and potassium currents in rat ventricle. Cardiovasc Res 27: 1795‐1799, 1993.
 115. Cohen SA . Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle. Presence in terminal intercalated disks. Circulation 94: 3083‐3086, 1996.
 116. Colecraft HM , Alseikhan B , Takahashi SX , Chaudhuri D , Mittman S , Yegnasubramanian V , Alvania RS , Johns DC , Marban E , Yue DT . Novel functional properties of Ca(2+) channel beta subunits revealed by their expression in adult rat heart cells. J Physiol 541: 435‐452, 2002.
 117. Coppen SR , Kodama I , Boyett MR , Dobrzynski H , Takagishi Y , Honjo H , Yeh HI , Severs NJ . Connexin45, a major connexin of the rabbit sinoatrial node, is co‐expressed with connexin43 in a restricted zone at the nodal‐crista terminalis border. J Histochem Cytochem 47: 907‐918, 1999.
 118. Coppen SR , Severs NJ , Gourdie RG . Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. Dev Genet 24: 82‐90, 1999.
 119. Cordeiro JM , Greene L , Heilmann C , Antzelevitch D , Antzelevitch C . Transmural heterogeneity of calcium activity and mechanical function in the canine left ventricle. Am J Physiol Heart Circ Physiol 286: H1471‐H1479, 2004.
 120. Cordeiro JM , Spitzer KW , Giles WR . Repolarizing K+ currents in rabbit heart Purkinje cells. J Physiol 508(Pt 3): 811‐823, 1998.
 121. Crisel RK , Farzaneh‐Far R , Na B , Whooley MA . First‐degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: Data from the Heart and Soul Study. Eur Heart J 32: 1875‐1880, 2011.
 122. Crotti L , Johnson CN , Graf E , De Ferrari GM , Cuneo BF , Ovadia M , Papagiannis J , Feldkamp MD , Rathi SG , Kunic JD , Pedrazzini M , Wieland T , Lichtner P , Beckmann BM , Clark T , Shaffer C , Benson DW , Kaab S , Meitinger T , Strom TM , Chazin WJ , Schwartz PJ , George AL, Jr . Calmodulin mutations associated with recurrent cardiac arrest in infants. Circulation 127: 1009‐1017, 2013.
 123. Cunha SR , Hund TJ , Hashemi S , Voigt N , Li N , Wright P , Koval O , Li J , Gudmundsson H , Gumina RJ , Karck M , Schott JJ , Probst V , Le Marec H , Anderson ME , Dobrev D , Wehrens XH , Mohler PJ . Defects in ankyrin‐based membrane protein targeting pathways underlie atrial fibrillation. Circulation 124: 1212‐1222, 2011.
 124. Curran J , Brown KH , Santiago DJ , Pogwizd S , Bers DM , Shannon TR . Spontaneous Ca waves in ventricular myocytes from failing hearts depend on Ca(2+)‐calmodulin‐dependent protein kinase II. J Mol Cell Cardiol 49: 25‐32, 2010.
 125. Curran J , Hinton MJ , Rios E , Bers DM , Shannon TR . Beta‐adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin‐dependent protein kinase. Circ Res 100: 391‐398, 2007.
 126. Curran ME , Splawski I , Timothy KW , Vincent GM , Green ED , Keating MT . A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 80: 795‐803, 1995.
 127. Currie S , Elliott EB , Smith GL , Loughrey CM . Two candidates at the heart of dysfunction: The ryanodine receptor and calcium/calmodulin protein kinase II as potential targets for therapeutic intervention‐An in vivo perspective. Pharmacol Ther 131: 204‐220, 2011.
 128. Currie S , Loughrey CM , Craig MA , Smith GL . Calcium/calmodulin‐dependent protein kinase IIdelta associates with the ryanodine receptor complex and regulates channel function in rabbit heart. Biochem J 377: 357‐366, 2004.
 129. Darbar D , Kannankeril PJ , Donahue BS , Kucera G , Stubblefield T , Haines JL , George AL, Jr. , Roden DM . Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation. Circulation 117: 1927‐1935, 2008.
 130. Davies MJ , Pomerance A . Quantitative study of ageing changes in the human sinoatrial node and internodal tracts. Br Heart J 34: 150‐152, 1972.
 131. Delpon E , Cordeiro JM , Nunez L , Thomsen PE , Guerchicoff A , Pollevick GD , Wu Y , Kanters JK , Larsen CT , Hofman‐Bang J , Burashnikov E , Christiansen M , Antzelevitch C . Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. Circ Arrhythm Electrophysiol 1: 209‐218, 2008.
 132. Deo M , Ruan Y , Pandit SV , Shah K , Berenfeld O , Blaufox A , Cerrone M , Noujaim SF , Denegri M , Jalife J , Priori SG . KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia. Proc Natl Acad Sci U S A 110: 4291‐4296, 2013.
 133. DePaoli AM , Bell GI , Stoffel M . G protein‐activated inwardly rectifying potassium channel (GIRK1/KGA) mRNA in adult rat heart and brain by in situ hybridization histochemistry. Mol Cell Neurosci 5: 515‐522, 1994.
 134. Dhamoon AS , Pandit SV , Sarmast F , Parisian KR , Guha P , Li Y , Bagwe S , Taffet SM , Anumonwo JM . Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current. Circ Res 94: 1332‐1339, 2004.
 135. Dhar Malhotra J , Chen C , Rivolta I , Abriel H , Malhotra R , Mattei LN , Brosius FC , Kass RS , Isom LL . Characterization of sodium channel alpha‐ and beta‐subunits in rat and mouse cardiac myocytes. Circulation 103: 1303‐1310, 2001.
 136. Di Diego JM , Sun ZQ , Antzelevitch C . I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium. Am J Physiol 271: H548‐H561, 1996.
 137. Difrancesco D . A new interpretation of the pace‐maker current in calf Purkinje fibres. J Physiol 314: 359‐376, 1981a.
 138. Difrancesco D . A study of the ionic nature of the pace‐maker current in calf Purkinje fibres. J Physiol 314: 377‐393, 1981b.
 139. DiFrancesco D , Noble D . The funny current has a major pacemaking role in the sinus node. Heart Rhythm 9: 299‐301, 2012.
 140. Dimmer C , Tavernier R , Gjorgov N , Van Nooten G , Clement DL , Jordaens L . Variations of autonomic tone preceding onset of atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 82: 22‐25, 1998.
 141. Dixon AK , Gubitz AK , Ashford ML , Richardson PJ , Freeman TC . Distribution of mRNA encoding the inwardly rectifying K+ channel, BIR1 in rat tissues. FEBS Lett 374: 135‐140, 1995.
 142. Dixon JE , Shi W , Wang HS , McDonald C , Yu H , Wymore RS , Cohen IS , McKinnon D . Role of the Kv4.3 K+ channel in ventricular muscle. A molecular correlate for the transient outward current. Circ Res 79: 659‐668, 1996.
 143. Dobrev D , Friedrich A , Voigt N , Jost N , Wettwer E , Christ T , Knaut M , Ravens U . The G protein‐gated potassium current IK,ACh is constitutively active in patients with chronic atrial fibrillation. Circulation 112: 3697‐3706, 2005.
 144. Dobrev D , Graf E , Wettwer E , Himmel HM , Hala O , Doerfel C , Christ T , Schuler S , Ravens U . Molecular basis of downregulation of G‐protein‐coupled inward rectifying K+ current (IK,ACh) in chronic human atrial fibrillation: Decrease in GIRK4 mRNA correlates with reduced IK,ACh and muscarinic receptor‐mediated shortening of action potentials. Circulation 104: 2551‐2557, 2001.
 145. Dobrev D , Nattel S . Calcium handling abnormalities in atrial fibrillation as a target for innovative therapeutics. J Cardiovasc Pharmacol 52: 293‐299, 2008.
 146. Dobrev D , Ravens U . Remodeling of cardiomyocyte ion channels in human atrial fibrillation. Basic Res Cardiol 98: 137‐148, 2003.
 147. Dobrev D , Voigt N , Wehrens XHT . The ryanodine receptor channel as a molecular motif in atrial fibrillation: Pathophysiological and therapeutic implications. Cardiovasc Res 89: 734‐743, 2011.
 148. Dobrzynski H , Anderson RH , Atkinson A , Borbas Z , D'Souza A , Fraser JF , Inada S , Logantha SJRJ , MONFREDI O , Morris GM , Moorman AFM , Nikolaidou T , Schneider H , Szuts V , Temple IP , Yanni J , Boyett MR . Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Pharmacol Ther 139: 260‐288, 2013.
 149. Dobrzynski H , Marples DD , Musa H , Yamanushi TT , Henderson Z , Takagishi Y , Honjo H , Kodama I , Boyett MR . Distribution of the muscarinic K+ channel proteins Kir3.1 and Kir3.4 in the ventricle, atrium, and sinoatrial node of heart. J Histochem Cytochem 49: 1221‐1234, 2001.
 150. Dobrzynski H , Nikolski VP , Sambelashvili AT , Greener ID , Yamamoto M , Boyett MR , Efimov IR . Site of origin and molecular substrate of atrioventricular junctional rhythm in the rabbit heart. Circ Res 93: 1102‐1110, 2003.
 151. Doupnik CA , Davidson N , Lester HA . The inward rectifier potassium channel family. Curr Opin Neurobiol 5: 268‐277, 1995.
 152. Dun W , Boyden PA . The Purkinje cell; 2008 style. J Mol Cell Cardiol 45: 617‐624, 2008.
 153. Dzhura I , Wu Y , Colbran RJ , Balser JR , Anderson ME . Calmodulin kinase determines calcium‐dependent facilitation of L‐type calcium channels. Nat Cell Biol 2: 173‐177, 2000.
 154. Edwards AG , Grandi E , Hake JE , Patel S , Li P , Miyamoto S , Omens JH , Brown JH , Bers DM , McCulloch AD . Nonequilibrium reactivation of the Na+ current drives early afterdepolarizations in mouse ventricle. Circ Arrhythm Electrophysiol 7: 1205‐1213, 2014.
 155. Ehrlich JR , Cha TJ , Zhang L , Chartier D , Melnyk P , Hohnloser SH , Nattel S . Cellular electrophysiology of canine pulmonary vein cardiomyocytes: Action potential and ionic current properties. J Physiol 551: 801‐813, 2003.
 156. Ehrlich JR , Nattel S , Hohnloser SH . Atrial fibrillation and congestive heart failure: Specific considerations at the intersection of two common and important cardiac disease sets. J Cardiovasc Electrophysiol 13: 399‐405, 2002.
 157. Eiras S , Narolska NA , van Loon RB , Boontje NM , Zaremba R , Jimenez CR , Visser FC , Stooker W , van der Velden J , Stienen GJ . Alterations in contractile protein composition and function in human atrial dilatation and atrial fibrillation. J Mol Cell Cardiol 41: 467‐477, 2006.
 158. El‐Armouche A , Boknik P , Eschenhagen T , Carrier L , Knaut M , Ravens U , Dobrev D . Molecular determinants of altered Ca2+ handling in human chronic atrial fibrillation. Circulation 114: 670‐680, 2006.
 159. Ellinghaus P , Scheubel RJ , Dobrev D , Ravens U , Holtz J , Huetter J , Nielsch U , Morawietz H . Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high‐density oligonucleotide arrays. J Thorac Cardiovasc Surg 129: 1383‐1390, 2005.
 160. Erickson JR , Joiner ML , Guan X , Kutschke W , Yang J , Oddis CV , Bartlett RK , Lowe JS , O'Donnell SE , Aykin‐Burns N , Zimmerman MC , Zimmerman K , Ham AJ , Weiss RM , Spitz DR , Shea MA , Colbran RJ , Mohler PJ , Anderson ME . A dynamic pathway for calcium‐independent activation of CaMKII by methionine oxidation. Cell 133: 462‐474, 2008.
 161. Eschenhagen T . Is ryanodine receptor phosphorylation key to the fight or flight response and heart failure? J Clin Invest 120: 4197‐4203, 2010.
 162. Faggiano P , d'Aloia A , Gualeni A , Gardini A , Giordano A . Mechanisms and immediate outcome of in‐hospital cardiac arrest in patients with advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 87: 655‐657, A610‐651, 2001.
 163. Fallavollita JA , Heavey BM , Luisi AJ, Jr. , Michalek SM , Baldwa S , Mashtare TL, Jr. , Hutson AD , Dekemp RA , Haka MS , Sajjad M , Cimato TR , Curtis AB , Cain ME , Canty JM, Jr . Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. J Am Coll Cardiol 63: 141‐149, 2014.
 164. Fedida D , Giles WR . Regional variations in action potentials and transient outward current in myocytes isolated from rabbit left ventricle. J Physiol 442: 191‐209, 1991.
 165. Fedorov VV , Glukhov AV , Chang R , Kostecki G , Aferol H , Hucker WJ , Wuskell JP , Loew LM , Schuessler RB , Moazami N , Efimov IR . Optical mapping of the isolated coronary‐perfused human sinus node. J Am Coll Cardiol 56: 1386‐1394, 2010.
 166. Fedorov VV , Schuessler RB , Hemphill M , Ambrosi CM , Chang R , Voloshina AS , Brown K , Hucker WJ , Efimov IR . Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria. Circ Res 104: 915‐923, 2009.
 167. Feng J , Yue L , Wang Z , Nattel S . Ionic mechanisms of regional action potential heterogeneity in the canine right atrium. Circ Res 83: 541‐551, 1998.
 168. Fermini B , Wang Z , Duan D , Nattel S . Differences in rate dependence of transient outward current in rabbit and human atrium. Am J Physiol 263: H1747‐H1754, 1992.
 169. Firek L , Giles WR . Outward currents underlying repolarization in human atrial myocytes. Cardiovasc Res 30: 31‐38, 1995.
 170. Fiset C , Clark RB , Shimoni Y , Giles WR . Shal‐type channels contribute to the Ca2+‐independent transient outward K+ current in rat ventricle. J Physiol 500(Pt 1): 51‐64, 1997.
 171. Flagg TP , Kurata HT , Masia R , Caputa G , Magnuson MA , Lefer DJ , Coetzee WA , Nichols CG . Differential structure of atrial and ventricular KATP: Atrial KATP channels require SUR1. Circ Res 103: 1458‐1465, 2008.
 172. Frank K , Kranias EG . Phospholamban and cardiac contractility. Ann Med 32: 572‐578, 2000.
 173. Fulop L , Banyasz T , Magyar J , Szentandrassy N , Varro A , Nanasi PP . Reopening of L‐type calcium channels in human ventricular myocytes during applied epicardial action potentials. Acta Physiol Scand 180: 39‐47, 2004.
 174. Furukawa T , Myerburg RJ , Furukawa N , Bassett AL , Kimura S . Differences in transient outward currents of feline endocardial and epicardial myocytes. Circ Res 67: 1287‐1291, 1990.
 175. Furushima H , Chinushi M , Okamura K , Iijima K , Komura S , Tanabe Y , Okada S , Izumi D , Aizawa Y . Comparison of conduction delay in the right ventricular outflow tract between Brugada syndrome and right ventricular cardiomyopathy: Investigation of signal average ECG in the precordial leads. Europace 9: 951‐956, 2007.
 176. Gaborit N , Le Bouter S , Szuts V , Varro A , Escande D , Nattel S , Demolombe S . Regional and tissue specific transcript signatures of ion channel genes in the non‐diseased human heart. J Physiol 582: 675‐693, 2007.
 177. Gao B , Sekido Y , Maximov A , Saad M , Forgacs E , Latif F , Wei MH , Lerman M , Lee JH , Perez‐Reyes E , Bezprozvanny I , Minna JD . Functional properties of a new voltage‐dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J Biol Chem 275: 12237‐12242, 2000.
 178. Gao G , Xie A , Huang SC , Zhou A , Zhang J , Herman AM , Ghassemzadeh S , Jeong EM , Kasturirangan S , Raicu M , Sobieski MA, II , Bhat G , Tatooles A , Benz EJ, Jr. , Kamp TJ , Dudley SC, Jr . Role of RBM25/LUC7L3 in abnormal cardiac sodium channel splicing regulation in human heart failure. Circulation 124: 1124‐1131, 2011.
 179. Gellens ME , George AL, Jr. , Chen LQ , Chahine M , Horn R , Barchi RL , Kallen RG . Primary structure and functional expression of the human cardiac tetrodotoxin‐insensitive voltage‐dependent sodium channel. Proc Natl Acad Sci U S A 89: 554‐558, 1992.
 180. George CH . Sarcoplasmic reticulum Ca2+ leak in heart failure: Mere observation or functional relevance? Cardiovasc Res 77: 302‐314, 2008.
 181. Giles WR , Imaizumi Y . Comparison of potassium currents in rabbit atrial and ventricular cells. J Physiol 405: 123‐145, 1988.
 182. Ginsburg KS , Bers DM . Modulation of excitation‐contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger. J Physiol 556: 463‐480, 2004.
 183. Giudicessi JR , Ye D , Tester DJ , Crotti L , Mugione A , Nesterenko VV , Albertson RM , Antzelevitch C , Schwartz PJ , Ackerman MJ . Transient outward current (I(to)) gain‐of‐function mutations in the KCND3‐encoded Kv4.3 potassium channel and Brugada syndrome. Heart Rhythm 8: 1024‐1032, 2011.
 184. Go AS , Mozaffarian D , Roger VL , Benjamin EJ , Berry JD , Blaha MJ , Dai S , Ford ES , Fox CS , Franco S , Fullerton HJ , Gillespie C , Hailpern SM , Heit JA , Howard VJ , Huffman MD , Judd SE , Kissela BM , Kittner SJ , Lackland DT , Lichtman JH , Lisabeth LD , Mackey RH , Magid DJ , Marcus GM , Marelli A , Matchar DB , McGuire DK , Mohler ER, III , Moy CS , Mussolino ME , Neumar RW , Nichol G , Pandey DK , Paynter NP , Reeves MJ , Sorlie PD , Stein J , Towfighi A , Turan TN , Virani SS , Wong ND , Woo D , Turner MB , American Heart Association Statistics C, Stroke Statistics S. Heart disease and stroke statistics–2014 update: A report from the American Heart Association. Circulation 129: e28‐e292, 2014.
 185. Gollob MH , Jones DL , Krahn AD , Danis L , Gong XQ , Shao Q , Liu X , Veinot JP , Tang AS , Stewart AF , Tesson F , Klein GJ , Yee R , Skanes AC , Guiraudon GM , Ebihara L , Bai D . Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation. N Engl J Med 354: 2677‐2688, 2006.
 186. Gonzalez de la Fuente M , Barana A , Gomez R , Amoros I , Dolz‐Gaiton P , Sacristan S , Atienza F , Pita A , Pinto A , Fernandez‐Aviles F , Caballero R , Tamargo J , Delpon E . Chronic atrial fibrillation up‐regulates beta1‐Adrenoceptors affecting repolarizing currents and action potential duration. Cardiovasc Res 97: 379‐388, 2013.
 187. Gorza L , Schiaffino S , Volpe P . Inositol 1,4,5‐trisphosphate receptor in heart: Evidence for its concentration in Purkinje myocytes of the conduction system. J Cell Biol 121: 345‐353, 1993.
 188. Gourdie RG , Severs NJ , Green CR , Rothery S , Germroth P , Thompson RP . The spatial distribution and relative abundance of gap‐junctional connexin40 and connexin43 correlate to functional properties of components of the cardiac atrioventricular conduction system. J Cell Sci 105(Pt 4): 985‐991, 1993.
 189. Grammer JB , Bosch RF , Kuhlkamp V , Seipel L . Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation. J Cardiovasc Electrophysiol 11: 626‐633, 2000.
 190. Grandi E , Bers DM . Models of the Ventricular Action Potential in Health and Disease. In: Zipes DP , Jalife J , editors. Cardiac Electrophysiology: From Cell to Bedside (6th ed). Saunders, 2013, pp. 319‐330.
 191. Grandi E , Pandit SV , Voigt N , Workman AJ , Dobrev D , Jalife J , Bers DM . Human atrial action potential and Ca2+ model: Sinus rhythm and chronic atrial fibrillation. Circ Res 109: 1055‐1066, 2011.
 192. Grandi E , Pasqualini FS , Bers DM . A novel computational model of the human ventricular action potential and Ca transient. J Mol Cell Cardiol 48: 112‐121, 2010.
 193. Grandi E , Puglisi JL , Wagner S , Maier LS , Severi S , Bers DM . Simulation of Ca‐calmodulin‐dependent protein kinase II on rabbit ventricular myocyte ion currents and action potentials. Biophys J 93: 3835‐3847, 2007.
 194. Grandi E , Workman AJ , Pandit SV . Altered excitationcContraction coupling in human chronic atrial fibrillation. J Atr Fibrillation 4: 37‐53, 2012.
 195. Greener ID , Monfredi O , Inada S , Chandler NJ , Tellez JO , Atkinson A , Taube M‐A , Billeter R , Anderson RH , Efimov IR , Molenaar P , Sigg DC , Sharma V , Boyett MR , Dobrzynski H . Molecular architecture of the human specialised atrioventricular conduction axis. J Mol Cell Cardiol 50: 642‐651, 2011.
 196. Greener ID , Tellez JO , Dobrzynski H , Yamamoto M , Graham GM , Billeter R , Boyett MR . Ion channel transcript expression at the rabbit atrioventricular conduction axis. Circ Arrhythm Electrophysiol 2: 305‐315, 2009.
 197. Greiser M , Neuberger HR , Harks E , El‐Armouche A , Boknik P , de Haan S , Verheyen F , Verheule S , Schmitz W , Ravens U , Nattel S , Allessie MA , Dobrev D , Schotten U . Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block‐induced atrial dilatation and atrial fibrillation. J Mol Cell Cardiol 46: 385‐394, 2009.
 198. Guerra JM , Everett THt , Lee KW , Wilson E , Olgin JE . Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation. Circulation 114: 110‐118, 2006.
 199. Guerrero PA , Schuessler RB , Davis LM , Beyer EC , Johnson CM , Yamada KA , Saffitz JE . Slow ventricular conduction in mice heterozygous for a connexin43 null mutation. J Clin Invest 99: 1991‐1998, 1997.
 200. Gui L , Bao Z , Jia Y , Qin X , Cheng ZJ , Zhu J , Chen QH . Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small‐conductance Ca2+‐activated K+ channels. Am J Physiol Heart Circ Physiol 304: H118‐H130, 2013.
 201. Guo W , Li H , Aimond F , Johns DC , Rhodes KJ , Trimmer JS , Nerbonne JM . Role of heteromultimers in the generation of myocardial transient outward K+ currents. Circ Res 90: 586‐593, 2002.
 202. Guo W , Li H , London B , Nerbonne JM . Functional consequences of elimination of i(to,f) and i(to,s): early afterdepolarizations, atrioventricular block, and ventricular arrhythmias in mice lacking Kv1.4 and expressing a dominant‐negative Kv4 alpha subunit. Circ Res 87: 73‐79, 2000.
 203. Gurney A , Manoury B . Two‐pore potassium channels in the cardiovascular system. Eur Biophys J 38: 305‐318, 2009.
 204. Gussak I , Chaitman BR , Kopecky SL , Nerbonne JM . Rapid ventricular repolarization in rodents: Electrocardiographic manifestations, molecular mechanisms, and clinical insights. J Electrocardiol 33: 159‐170, 2000.
 205. Hagendorff A , Schumacher B , Kirchhoff S , Luderitz B , Willecke K . Conduction disturbances and increased atrial vulnerability in Connexin40‐deficient mice analyzed by transesophageal stimulation. Circulation 99: 1508‐1515, 1999.
 206. Hagiwara N , Irisawa H , Kameyama M . Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino‐atrial node cells. J Physiol 395: 233‐253, 1988.
 207. Handrock R , Schroder F , Hirt S , Haverich A , Mittmann C , Herzig S . Single‐channel properties of L‐type calcium channels from failing human ventricle. Cardiovasc Res 37: 445‐455, 1998.
 208. Hao X , Zhang Y , Zhang X , Nirmalan M , Davies L , Konstantinou D , Yin F , Dobrzynski H , Wang X , Grace A , Zhang H , Boyett M , Huang CLH , Lei M . TGF‐β1‐mediated fibrosis and ion channel remodeling are key mechanisms in producing the sinus node dysfunction associated with SCN5A deficiency and aging. Circ Arrhythm Electrophysiol 4: 397‐406, 2011.
 209. He K , Shi X , Zhang X , Dang S , Ma X , Liu F , Xu M , Lv Z , Han D , Fang X , Zhang Y . Long‐distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes. Cardiovasc Res 92: 39‐47, 2011.
 210. Heath BM , Terrar DA . The deactivation kinetics of the delayed rectifier components IKr and IKs in guinea‐pig isolated ventricular myocytes. Exp Physiol 81: 605‐621, 1996a.
 211. Heath BM , Terrar DA . Separation of the components of the delayed rectifier potassium current using selective blockers of IKr and IKs in guinea‐pig isolated ventricular myocytes. Exp Physiol 81: 587‐603, 1996b.
 212. Heijman J , Spatjens RL , Seyen SR , Lentink V , Kuijpers HJ , Boulet IR , de Windt LJ , David M , Volders PG . Dominant‐negative control of cAMP‐dependent IKs upregulation in human long‐QT syndrome type 1. Circ Res 110: 211‐219, 2012.
 213. Herren AW , Bers DM , Grandi E . Post‐translational modifications of the cardiac Na channel: Contribution of CaMKII‐dependent phosphorylation to acquired arrhythmias. Am J Physiol Heart Circ Physiol 305: H431‐H445, 2013.
 214. Himmel HM , Wettwer E , Li Q , Ravens U . Four different components contribute to outward current in rat ventricular myocytes. Am J Physiol 277: H107‐H118, 1999.
 215. Hirano Y , Moscucci A , January CT . Direct measurement of L‐type Ca2+ window current in heart cells. Circ Res 70: 445‐455, 1992.
 216. Hiraoka M , Kawano S . Calcium‐sensitive and insensitive transient outward current in rabbit ventricular myocytes. J Physiol 410: 187‐212, 1989.
 217. Hobai IA , O'Rourke B . Enhanced Ca(2+)‐activated Na(+)‐Ca(2+) exchange activity in canine pacing‐induced heart failure. Circ Res 87: 690‐698, 2000.
 218. Hobai IA , O'Rourke B . Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation‐contraction coupling in canine heart failure. Circulation 103: 1577‐1584, 2001.
 219. Hoch B , Meyer R , Hetzer R , Krause EG , Karczewski P . Identification and expression of delta‐isoforms of the multifunctional Ca2+/calmodulin‐dependent protein kinase in failing and nonfailing human myocardium. Circ Res 84: 713‐721, 1999.
 220. Hodgson‐Zingman DM , Karst ML , Zingman LV , Heublein DM , Darbar D , Herron KJ , Ballew JD , de Andrade M , Burnett JC, Jr. , Olson TM . Atrial natriuretic peptide frameshift mutation in familial atrial fibrillation. N Engl J Med 359: 158‐165, 2008.
 221. Holzem KM , Efimov IR . Arrhythmogenic remodelling of activation and repolarization in the failing human heart. Europace 14 (Suppl 5): v50‐v57, 2012.
 222. Hong K , Piper DR , Diaz‐Valdecantos A , Brugada J , Oliva A , Burashnikov E , Santos‐de‐Soto J , Grueso‐Montero J , Diaz‐Enfante E , Brugada P , Sachse F , Sanguinetti MC , Brugada R . De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovasc Res 68: 433‐440, 2005.
 223. Honjo H , Boyett MR , Coppen SR , Takagishi Y , Opthof T , Severs NJ , Kodama I . Heterogeneous expression of connexins in rabbit sinoatrial node cells: Correlation between connexin isotype and cell size. Cardiovasc Res 53: 89‐96, 2002.
 224. Honjo H , Boyett MR , Kodama I , Toyama J . Correlation between electrical activity and the size of rabbit sino‐atrial node cells. J Physiol 496(Pt 3): 795‐808, 1996.
 225. Horie M , Hayashi S , Kawai C . Two types of delayed rectifying K+ channels in atrial cells of guinea pig heart. Jpn J Physiol 40: 479‐490, 1990.
 226. Hove‐Madsen L , Llach A , Bayes‐Genis A , Roura S , Rodriguez Font E , Aris A , Cinca J . Atrial fibrillation is associated with increased spontaneous calcium release from the sarcoplasmic reticulum in human atrial myocytes. Circulation 110: 1358‐1363, 2004.
 227. Hsieh YC , Chang PC , Hsueh CH , Lee YS , Shen C , Weiss JN , Chen Z , Ai T , Lin SF , Chen PS . Apamin‐sensitive potassium current modulates action potential duration restitution and arrhythmogenesis of failing rabbit ventricles. Circ Arrhythm Electrophysiol 6: 410‐418, 2013.
 228. Hu D , Barajas‐Martinez H , Burashnikov E , Springer M , Wu Y , Varro A , Pfeiffer R , Koopmann TT , Cordeiro JM , Guerchicoff A , Pollevick GD , Antzelevitch C . A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. Circ Cardiovasc Genet 2: 270‐278, 2009.
 229. Huang B , Wang S , Qin D , Boutjdir M , El‐Sherif N . Diminished basal phosphorylation level of phospholamban in the postinfarction remodeled rat ventricle: Role of beta‐adrenergic pathway, G(i) protein, phosphodiesterase, and phosphatases. Circ Res 85: 848‐855, 1999.
 230. Hucker WJ , Sharma V , Nikolski VP , Efimov IR . Atrioventricular conduction with and without AV nodal delay: Two pathways to the bundle of His in the rabbit heart. Am J Physiol Heart Circ Physiol 293: H1122‐H1130, 2007.
 231. Hullin R , Khan IF , Wirtz S , Mohacsi P , Varadi G , Schwartz A , Herzig S . Cardiac L‐type calcium channel beta‐subunits expressed in human heart have differential effects on single channel characteristics. J Biol Chem 278: 21623‐21630, 2003.
 232. Hullin R , Singer‐Lahat D , Freichel M , Biel M , Dascal N , Hofmann F , Flockerzi V . Calcium channel beta subunit heterogeneity: Functional expression of cloned cDNA from heart, aorta and brain. Embo J 11: 885‐890, 1992.
 233. Inada S , Hancox JC , Zhang H , Boyett MR . One‐dimensional mathematical model of the atrioventricular node including atrio‐nodal, nodal, and nodal‐his cells. Biophys J 97: 2117‐2127, 2009.
 234. Inoue M , Imanaga I . Masking of A‐type K+ channel in guinea pig cardiac cells by extracellular Ca2+ . Am J Physiol 264: C1434‐C1438, 1993.
 235. Isomoto S , Kurachi Y . Function, regulation, pharmacology, and molecular structure of ATP‐sensitive K+ channels in the cardiovascular system. J Cardiovasc Electrophysiol 8: 1431‐1446, 1997.
 236. Jalife J . Deja vu in the theories of atrial fibrillation dynamics. Cardiovasc Res 89: 766‐775, 2011.
 237. Janse MJ , Sosunov EA , Coronel R , Opthof T , Anyukhovsky EP , de Bakker JM , Plotnikov AN , Shlapakova IN , Danilo P, Jr. , Tijssen JG , Rosen MR . Repolarization gradients in the canine left ventricle before and after induction of short‐term cardiac memory. Circulation 112: 1711‐1718, 2005.
 238. Janse MJ , Wit AL . Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 69: 1049‐1169, 1989.
 239. January CT , Riddle JM . Early afterdepolarizations: Mechanism of induction and block. A role for L‐type Ca2+ current. Circ Res 64: 977‐990, 1989.
 240. Jones SA , Boyett MR , Lancaster MK . Declining into failure: The age‐dependent loss of the L‐type calcium channel within the sinoatrial node. Circulation 115: 1183‐1190, 2007.
 241. Jones SA , Lancaster MK , Boyett MR . Ageing‐related changes of connexins and conduction within the sinoatrial node. J Physiol 560: 429‐437, 2004.
 242. Josephson IR , Sanchez‐Chapula J , Brown AM . Early outward current in rat single ventricular cells. Circ Res 54: 157‐162, 1984.
 243. Jost N , Papp JG , Varro A . Slow delayed rectifier potassium current (IKs) and the repolarization reserve. Ann Noninvasive Electrocardiol 12: 64‐78, 2007.
 244. Jost N , Virag L , Bitay M , Takacs J , Lengyel C , Biliczki P , Nagy Z , Bogats G , Lathrop DA , Papp JG , Varro A . Restricting excessive cardiac action potential and QT prolongation: A vital role for IKs in human ventricular muscle. Circulation 112: 1392‐1399, 2005.
 245. Jost N , Virag L , Comtois P , Ordog B , Szuts V , Seprenyi G , Bitay M , Kohajda Z , Koncz I , Nagy N , Szel T , Magyar J , Kovacs M , Puskas LG , Lengyel C , Wettwer E , Ravens U , Nanasi PP , Papp JG , Varro A , Nattel S . Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs. J Physiol 591: 4189‐4206, 2013.
 246. Kaab S , Dixon J , Duc J , Ashen D , Nabauer M , Beuckelmann DJ , Steinbeck G , McKinnon D , Tomaselli GF . Molecular basis of transient outward potassium current downregulation in human heart failure: A decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 98: 1383‐1393, 1998.
 247. Kaab S , Nuss HB , Chiamvimonvat N , O'Rourke B , Pak PH , Kass DA , Marban E , Tomaselli GF . Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing‐induced heart failure. Circ Res 78: 262‐273, 1996.
 248. Kaese S , Verheule S . Cardiac electrophysiology in mice: A matter of size. Front Physiol 3: 345, 2012.
 249. Kanazawa H , Ieda M , Kimura K , Arai T , Kawaguchi‐Manabe H , Matsuhashi T , Endo J , Sano M , Kawakami T , Kimura T , Monkawa T , Hayashi M , Iwanami A , Okano H , Okada Y , Ishibashi‐Ueda H , Ogawa S , Fukuda K . Heart failure causes cholinergic transdifferentiation of cardiac sympathetic nerves via gp130‐signaling cytokines in rodents. J Clin Invest 120: 408‐421, 2010.
 250. Kane GC , Behfar A , Dyer RB , O'Cochlain DF , Liu XK , Hodgson DM , Reyes S , Miki T , Seino S , Terzic A . KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension. Hum Mol Genet 15: 2285‐2297, 2006.
 251. Kanter HL , Laing JG , Beau SL , Beyer EC , Saffitz JE . Distinct patterns of connexin expression in canine Purkinje fibers and ventricular muscle. Circ Res 72: 1124‐1131, 1993.
 252. Kass RS , Sanguinetti MC . Inactivation of calcium channel current in the calf cardiac Purkinje fiber. Evidence for voltage‐ and calcium‐mediated mechanisms. J Gen Physiol 84: 705‐726, 1984.
 253. Kato T , Iwasaki YK , Nattel S . Connexins and atrial fibrillation: Filling in the gaps. Circulation 125: 203‐206, 2012.
 254. Kattygnarath D , Maugenre S , Neyroud N , Balse E , Ichai C , Denjoy I , Dilanian G , Martins RP , Fressart V , Berthet M , Schott JJ , Leenhardt A , Probst V , Le Marec H , Hainque B , Coulombe A , Hatem SN , Guicheney P . MOG1: A new susceptibility gene for Brugada syndrome. Circ Cardiovasc Genet 4: 261‐268, 2011.
 255. Keith A , Flack M . The form and nature of the muscular connections between the primary divisions of the vertebrate heart. J Anat Physiol 41: 172‐189, 1907.
 256. Kirchhefer U , Schmitz W , Scholz H , Neumann J . Activity of cAMP‐dependent protein kinase and Ca2+/calmodulin‐dependent protein kinase in failing and nonfailing human hearts. Cardiovasc Res 42: 254‐261, 1999.
 257. Kirchhof CJ , Bonke FI , Allessie MA . Evidence for the presence of electrotonic depression of pacemakers in the rabbit atrioventricular node. The effects of uncoupling from the surrounding myocardium. Basic Res Cardiol 83: 190‐201, 1988.
 258. Kiss E , Ball NA , Kranias EG , Walsh RA . Differential changes in cardiac phospholamban and sarcoplasmic reticular Ca(2+)‐ATPase protein levels. Effects on Ca2+ transport and mechanics in compensated pressure‐overload hypertrophy and congestive heart failure. Circ Res 77: 759‐764, 1995.
 259. Kjekshus J . Arrhythmias and mortality in congestive heart failure. Am J Cardiol 65: 42I‐48I, 1990.
 260. Kline RP , Kupersmith J . Effects of extracellular potassium accumulation and sodium pump activation on automatic canine Purkinje fibres. J Physiol 324: 507‐533, 1982.
 261. Kneller J , Kalifa J , Zou R , Zaitsev AV , Warren M , Berenfeld O , Vigmond EJ , Leon LJ , Nattel S , Jalife J . Mechanisms of atrial fibrillation termination by pure sodium channel blockade in an ionically‐realistic mathematical model. Circ Res 96: e35‐e47, 2005.
 262. Kodama I , Nikmaram MR , Boyett MR , Suzuki R , Honjo H , Owen JM . Regional differences in the role of the Ca2+ and Na+ currents in pacemaker activity in the sinoatrial node. Am J Physiol 272: H2793‐H2806, 1997.
 263. Kong W , Po S , Yamagishi T , Ashen MD , Stetten G , Tomaselli GF . Isolation and characterization of the human gene encoding Ito: Further diversity by alternative mRNA splicing. Am J Physiol 275: H1963‐H1970, 1998.
 264. Kucera JP , Rohr S , Rudy Y . Localization of sodium channels in intercalated disks modulates cardiac conduction. Circ Res 91: 1176‐1182, 2002.
 265. Kuo HC , Cheng CF , Clark RB , Lin JJ , Lin JL , Hoshijima M , Nguyen‐Tran VT , Gu Y , Ikeda Y , Chu PH , Ross J , Giles WR , Chien KR . A defect in the Kv channel‐interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia. Cell 107: 801‐813, 2001.
 266. Kurita T , Shimizu W , Inagaki M , Suyama K , Taguchi A , Satomi K , Aihara N , Kamakura S , Kobayashi J , Kosakai Y . The electrophysiologic mechanism of ST‐segment elevation in Brugada syndrome. J Am Coll Cardiol 40: 330‐334, 2002.
 267. Kuryshev YA , Brittenham GM , Fujioka H , Kannan P , Shieh CC , Cohen SA , Brown AM . Decreased sodium and increased transient outward potassium currents in iron‐loaded cardiac myocytes. Implications for the arrhythmogenesis of human siderotic heart disease. Circulation 100: 675‐683, 1999.
 268. Kusumoto FM , Phillips R , Goldschlager N . Pacing therapy in the elderly. Am J Geriatr Cardiol 11: 305‐316, 2002.
 269. Kyndt F , Probst V , Potet F , Demolombe S , Chevallier JC , Baro I , Moisan JP , Boisseau P , Schott JJ , Escande D , Le Marec H . Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family. Circulation 104: 3081‐3086, 2001.
 270. Lahat H , Pras E , Olender T , Avidan N , Ben‐Asher E , Man O , Levy‐Nissenbaum E , Khoury A , Lorber A , Goldman B , Lancet D , Eldar M . A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine‐induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Gen 69: 1378‐1384, 2001.
 271. Lai LP , Su MJ , Lin JL , Tsai CH , Lin FY , Chen YS , Hwang JJ , Huang SK , Tseng YZ , Lien WP . Measurement of funny current (If) channel mRNA in human atrial tissue: Correlation with left atrial filling pressure and atrial fibrillation. J Cardiovasc Electrophysiol 10: 947‐953, 1999.
 272. Lakatta EG , DiFrancesco D . What keeps us ticking: A funny current, a calcium clock, or both? J Mol Cell Cardiol 47: 157‐170, 2009.
 273. Lakatta EG , Maltsev VA , Vinogradova TM . A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker. Circ Res 106: 659‐673, 2010.
 274. Larsen AP , Olesen SP , Grunnet M , Jespersen T . Characterization of hERG1a and hERG1b potassium channels‐a possible role for hERG1b in the I (Kr) current. Pflugers Arch 456: 1137‐1148, 2008.
 275. Laurent G , Leong‐Poi H , Mangat I , Moe GW , Hu X , So PP , Tarulli E , Ramadeen A , Rossman EI , Hennan JK , Dorian P . Effects of chronic gap junction conduction‐enhancing antiarrhythmic peptide GAP‐134 administration on experimental atrial fibrillation in dogs. Circ Arrhythm Electrophysiol 2: 171‐178, 2009.
 276. Le Scouarnec S , Bhasin N , Vieyres C , Hund TJ , Cunha SR , Koval O , Marionneau C , Chen B , Wu Y , Demolombe S , Song L‐S , Le Marec H , Probst V , Schott J‐J , Anderson ME , Mohler PJ . Dysfunction in ankyrin‐B‐dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci U S A 105: 15617‐15622, 2008.
 277. Lee HC , Rudy Y , Po‐Yuan P , Sheu SH , Chang JG , Cui J . Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization. Heart Rhythm 10: 1220‐1228, 2013.
 278. Lei M , Jones SA , Liu J , Lancaster MK , Fung SS , Dobrzynski H , Camelliti P , Maier SK , Noble D , Boyett MR . Requirement of neuronal‐ and cardiac‐type sodium channels for murine sinoatrial node pacemaking. J Physiol 559: 835‐848, 2004.
 279. Lengyel C , Iost N , Virag L , Varro A , Lathrop DA , Papp JG . Pharmacological block of the slow component of the outward delayed rectifier current (I(Ks)) fails to lengthen rabbit ventricular muscle QT(c) and action potential duration. Br J Pharmacol 132: 101‐110, 2001.
 280. Lev M . Aging changes in the human sinoatrial node. J Gerontol 9: 1‐9, 1954.
 281. Li D , Zhang L , Kneller J , Nattel S . Potential ionic mechanism for repolarization differences between canine right and left atrium. Circ Res 88: 1168‐1175, 2001.
 282. Li GR , Feng J , Yue L , Carrier M . Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle. Am J Physiol 275: H369‐H377, 1998.
 283. Li GR , Feng J , Yue L , Carrier M , Nattel S . Evidence for two components of delayed rectifier K+ current in human ventricular myocytes. Circ Res 78: 689‐696, 1996.
 284. Li GR , Lau CP , Ducharme A , Tardif JC , Nattel S . Transmural action potential and ionic current remodeling in ventricles of failing canine hearts. Am J Physiol Heart Circ Physiol 283: H1031‐H1041, 2002.
 285. Li GR , Lau CP , Leung TK , Nattel S . Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles. Heart Rhythm 1: 460‐468, 2004.
 286. Li GR , Nattel S . Properties of human atrial ICa at physiological temperatures and relevance to action potential. Am J Physiol 272: H227‐H235, 1997.
 287. Li J , Greener ID , Inada S , Nikolski VP , Yamamoto M , Hancox JC , Zhang H , Billeter R , Efimov IR , Dobrzynski H , Boyett MR . Computer three‐dimensional reconstruction of the atrioventricular node. Circ Res 102: 975‐985, 2008.
 288. Li N , Timofeyev V , Tuteja D , Xu D , Lu L , Zhang Q , Zhang Z , Singapuri A , Albert TR , Rajagopal AV , Bond CT , Periasamy M , Adelman J , Chiamvimonvat N . Ablation of a Ca2+‐activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation. J Physiol 587: 1087‐1100, 2009.
 289. Li X , Zima AV , Sheikh F , Blatter LA , Chen J . Endothelin‐1‐induced arrhythmogenic Ca2+ signaling is abolished in atrial myocytes of inositol‐1,4,5‐trisphosphate(IP3)‐receptor type 2‐deficient mice. Circ Res 96: 1274‐1281, 2005.
 290. Li Y , Kranias EG , Mignery GA , Bers DM . Protein kinase A phosphorylation of the ryanodine receptor does not affect calcium sparks in mouse ventricular myocytes. Circ Res 90: 309‐316, 2002.
 291. Liang X , Xie H , Zhu PH , Hu J , Zhao Q , Wang CS , Yang C . Ryanodine receptor‐mediated Ca2+ events in atrial myocytes of patients with atrial fibrillation. Cardiology 111: 102‐110, 2008.
 292. Limberg SH , Netter MF , Rolfes C , Rinne S , Schlichthorl G , Zuzarte M , Vassiliou T , Moosdorf R , Wulf H , Daut J , Sachse FB , Decher N . TASK‐1 channels may modulate action potential duration of human atrial cardiomyocytes. Cell Physiol Biochem 28: 613‐624, 2011.
 293. Lin J , Keener JP . Modeling electrical activity of myocardial cells incorporating the effects of ephaptic coupling. Proc Natl Acad Sci U S A 107: 20935‐20940, 2010.
 294. Litovsky SH , Antzelevitch C . Transient outward current prominent in canine ventricular epicardium but not endocardium. Circ Res 62: 116‐126, 1988.
 295. Liu DW , Antzelevitch C . Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. Circ Res 76: 351‐365, 1995.
 296. Liu DW , Gintant GA , Antzelevitch C . Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 72: 671‐687, 1993.
 297. Liu GX , Derst C , Schlichthorl G , Heinen S , Seebohm G , Bruggemann A , Kummer W , Veh RW , Daut J , Preisig‐Muller R . Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea‐pig cardiomyocytes. J Physiol 532: 115‐126, 2001.
 298. Liu XK , Yamada S , Kane GC , Alekseev AE , Hodgson DM , O'Cochlain F , Jahangir A , Miki T , Seino S , Terzic A . Genetic disruption of Kir6.2, the pore‐forming subunit of ATP‐sensitive K+ channel, predisposes to catecholamine‐induced ventricular dysrhythmia. Diabetes 53(Suppl 3): S165‐168, 2004.
 299. London B , Michalec M , Mehdi H , Zhu X , Kerchner L , Sanyal S , Viswanathan PC , Pfahnl AE , Shang LL , Madhusudanan M , Baty CJ , Lagana S , Aleong R , Gutmann R , Ackerman MJ , McNamara DM , Weiss R , Dudley SC, Jr . Mutation in glycerol‐3‐phosphate dehydrogenase 1 like gene (GPD1‐L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation 116: 2260‐2268, 2007.
 300. London B , Trudeau MC , Newton KP , Beyer AK , Copeland NG , Gilbert DJ , Jenkins NA , Satler CA , Robertson GA . Two isoforms of the mouse ether‐a‐go‐go‐related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current. Circ Res 81: 870‐878, 1997.
 301. Lopatin AN , Nichols CG . Inward rectifiers in the heart: An update on I(K1). J Mol Cell Cardiol 33: 625‐638, 2001.
 302. Lundby A , Ravn LS , Svendsen JH , Hauns S , Olesen SP , Schmitt N . KCNE3 mutation V17M identified in a patient with lone atrial fibrillation. Cell Physiol Biochem 21: 47‐54, 2008.
 303. Lundquist AL , Manderfield LJ , Vanoye CG , Rogers CS , Donahue BS , Chang PA , Drinkwater DC , Murray KT , George AL, Jr . Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks). J Mol Cell Cardiol 38: 277‐287, 2005.
 304. Lundquist AL , Turner CL , Ballester LY , George AL , Jr . Expression and transcriptional control of human KCNE genes. Genomics 87: 119‐128, 2006.
 305. Machida T , Hashimoto N , Kuwahara I , Ogino Y , Matsuura J , Yamamoto W , Itano Y , Zamma A , Matsumoto R , Kamon J , Kobayashi T , Ishiwata N , Yamashita T , Ogura T , Nakaya H . Effects of a highly selective acetylcholine‐activated K+ channel blocker on experimental atrial fibrillation. Circ Arrhythm Electrophysiol 4: 94‐102, 2011.
 306. Mahida S . Expanding role of SK channels in cardiac electrophysiology. Heart Rhythm 11: 1233‐1238, 2014.
 307. Mahida S , Lubitz SA , Rienstra M , Milan DJ , Ellinor PT . Monogenic atrial fibrillation as pathophysiological paradigms. Cardiovasc Res 89: 692‐700, 2011.
 308. Mahida S , Mills RW , Tucker NR , Simonson B , Macri V , Lemoine MD , Das S , Milan DJ , Ellinor PT . Overexpression of KCNN3 results in sudden cardiac death. Cardiovasc Res 101: 326‐334, 2014.
 309. Maier LS , Barckhausen P , Weisser J , Aleksic I , Baryalei M , Pieske B . Ca2+ handling in isolated human atrial myocardium. Am J Physiol Heart Circ Physiol 279: H952‐H958, 2000.
 310. Maier LS , Zhang T , Chen L , DeSantiago J , Brown JH , Bers DM . Transgenic CaMKIIdeltaC overexpression uniquely alters cardiac myocyte Ca2+ handling: Reduced SR Ca2+ load and activated SR Ca2+ release. Circ Res 92: 904‐911, 2003.
 311. Maier SK , Westenbroek RE , Yamanushi TT , Dobrzynski H , Boyett MR , Catterall WA , Scheuer T . An unexpected requirement for brain‐type sodium channels for control of heart rate in the mouse sinoatrial node. Proc Natl Acad Sci U S A 100: 3507‐3512, 2003.
 312. Maltsev VA , Lakatta EG . The funny current in the context of the coupled‐clock pacemaker cell system. Heart Rhythm 9: 302‐307, 2012.
 313. Mangoni ME , Couette B , Bourinet E , Platzer J , Reimer D , Striessnig J , Nargeot J . Functional role of L‐type Cav1.3 Ca2+ channels in cardiac pacemaker activity. Proc Natl Acad Sci U S A 100: 5543‐5548, 2003.
 314. Marionneau C , Couette B , Liu J , Li H , Mangoni ME , Nargeot J , Lei M , Escande D , Demolombe S . Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart. J Physiol 562: 223‐234, 2005.
 315. Martinez ML , Heredia MP , Delgado C . Expression of T‐type Ca(2+) channels in ventricular cells from hypertrophied rat hearts. J Mol Cell Cardiol 31: 1617‐1625, 1999.
 316. Marx SO , Kurokawa J , Reiken S , Motoike H , D'Armiento J , Marks AR , Kass RS . Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1‐KCNE1 potassium channel. Science 295: 496‐499, 2002.
 317. Marx SO , Reiken S , Hisamatsu Y , Jayaraman T , Burkhoff D , Rosemblit N , Marks AR . PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 101: 365‐376, 2000.
 318. Matsuyama T‐a , Inoue S , Kobayashi Y , Sakai T , Saito T , Katagiri T , Ota H . Anatomical diversity and age‐related histological changes in the human right atrial posterolateral wall. Europace 6: 307‐315, 2004.
 319. McDonald TV , Yu Z , Ming Z , Palma E , Meyers MB , Wang KW , Goldstein SA , Fishman GI . A minK‐HERG complex regulates the cardiac potassium current I(Kr). Nature 388: 289‐292, 1997.
 320. Medeiros‐Domingo A , Kaku T , Tester DJ , Iturralde‐Torres P , Itty A , Ye B , Valdivia C , Ueda K , Canizales‐Quinteros S , Tusie‐Luna MT , Makielski JC , Ackerman MJ . SCN4B‐encoded sodium channel beta4 subunit in congenital long‐QT syndrome. Circulation 116: 134‐142, 2007.
 321. Medeiros‐Domingo A , Tan BH , Crotti L , Tester DJ , Eckhardt L , Cuoretti A , Kroboth SL , Song C , Zhou Q , Kopp D , Schwartz PJ , Makielski JC , Ackerman MJ . Gain‐of‐function mutation S422L in the KCNJ8‐encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J‐wave syndromes. Heart Rhythm 7: 1466‐1471, 2010.
 322. Melnyk P , Ehrlich JR , Pourrier M , Villeneuve L , Cha TJ , Nattel S . Comparison of ion channel distribution and expression in cardiomyocytes of canine pulmonary veins versus left atrium. Cardiovasc Res 65: 104‐116, 2005.
 323. Miake J , Marbán E , Nuss HB . Biological pacemaker created by gene transfer. Nature 419: 132‐133, 2002.
 324. Mihm MJ , Yu F , Carnes CA , Reiser PJ , McCarthy PM , Van Wagoner DR , Bauer JA . Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 104: 174‐180, 2001.
 325. Milanesi R , Baruscotti M , Gnecchi‐Ruscone T , DiFrancesco D . Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. N Engl J Med 354: 151‐157, 2006.
 326. Mitcheson JS , Sanguinetti MC . Biophysical properties and molecular basis of cardiac rapid and slow delayed rectifier potassium channels. Cell Physiol Biochem 9: 201‐216, 1999.
 327. Moe GK , Preston JB , Burlington H . Physiologic evidence for a dual A‐V transmission system. Circ Res 4: 357‐375, 1956.
 328. Mohler PJ , Gramolini AO , Bennett V . Ankyrins. J Cell Sci 115: 1565‐1566, 2002.
 329. Mohler PJ , Schott JJ , Gramolini AO , Dilly KW , Guatimosim S , duBell WH , Song LS , Haurogne K , Kyndt F , Ali ME , Rogers TB , Lederer WJ , Escande D , Le Marec H , Bennett V . Ankyrin‐B mutation causes type 4 long‐QT cardiac arrhythmia and sudden cardiac death. Nature 421: 634‐639, 2003.
 330. Mond HG , Proclemer A . The 11th world survey of cardiac pacing and implantable cardioverter‐defibrillators: Calendar year 2009—A World Society of Arrhythmia's project. Pacing Clin Electrophysiol 34: 1013‐1027, 2011.
 331. Mori Y , Fishman GI , Peskin CS . Ephaptic conduction in a cardiac strand model with 3D electrodiffusion. Proc Natl Acad Sci U S A 105: 6463‐6468, 2008.
 332. Morita H , Fukushima‐Kusano K , Nagase S , Takenaka‐Morita S , Nishii N , Kakishita M , Nakamura K , Emori T , Matsubara H , Ohe T . Site‐specific arrhythmogenesis in patients with Brugada syndrome. J Cardiovasc Electrophysiol 14: 373‐379, 2003.
 333. Morita H , Kusano‐Fukushima K , Nagase S , Fujimoto Y , Hisamatsu K , Fujio H , Haraoka K , Kobayashi M , Morita ST , Nakamura K , Emori T , Matsubara H , Hina K , Kita T , Fukatani M , Ohe T . Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol 40: 1437‐1444, 2002.
 334. Morotti S , Edwards AG , McCulloch AD , Bers DM , Grandi E . A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII. J Physiol 592: 1181‐1197, 2014.
 335. Morotti S , Grandi E , Summa A , Ginsburg KS , Bers DM . Theoretical study of L‐type Ca(2+) current inactivation kinetics during action potential repolarization and early afterdepolarizations. J Physiol 590: 4465‐4481, 2012.
 336. Mukherjee R , Spinale FG . L‐type calcium channel abundance and function with cardiac hypertrophy and failure: A review. J Mol Cell Cardiol 30: 1899‐1916, 1998.
 337. Munk AA , Adjemian RA , Zhao J , Ogbaghebriel A , Shrier A . Electrophysiological properties of morphologically distinct cells isolated from the rabbit atrioventricular node. J Physiol 493 (Pt 3): 801‐818, 1996.
 338. Myles RC , Wang L , Bers DM , Ripplinger CM . Decreased IK1 and increased ryanodine receptor sensitivity synergistically contribute to sustained focal arrhythmia in the intact rabbit heart. J Physiol, 2014 [Epub ahead of print].
 339. Myles RC , Wang L , Kang C , Bers DM , Ripplinger CM . Local beta‐adrenergic stimulation overcomes source‐sink mismatch to generate focal arrhythmia. Circ Res 110: 1454‐1464, 2012.
 340. Nabauer M , Beuckelmann DJ , Erdmann E . Characteristics of transient outward current in human ventricular myocytes from patients with terminal heart failure. Circ Res 73: 386‐394, 1993.
 341. Nabauer M , Beuckelmann DJ , Uberfuhr P , Steinbeck G . Regional differences in current density and rate‐dependent properties of the transient outward current in subepicardial and subendocardial myocytes of human left ventricle. Circulation 93: 168‐177, 1996.
 342. Nagy N , Szuts V , Horvath Z , Seprenyi G , Farkas AS , Acsai K , Prorok J , Bitay M , Kun A , Pataricza J , Papp JG , Nanasi PP , Varro A , Toth A . Does small‐conductance calcium‐activated potassium channel contribute to cardiac repolarization? J Mol Cell Cardiol 47: 656‐663, 2009.
 343. Nattel S , Burstein B , Dobrev D . Atrial remodeling and atrial fibrillation. Circ Arrhythm Electrophysiol 1: 62‐73, 2008.
 344. Nattel S , Maguy A , Le Bouter S , Yeh YH . Arrhythmogenic ion‐channel remodeling in the heart: Heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87: 425‐456, 2007.
 345. Neef S , Dybkova N , Sossalla S , Ort KR , Fluschnik N , Neumann K , Seipelt R , Schondube FA , Hasenfuss G , Maier LS . CaMKII‐dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation. Circ Res 106: 1134‐1144, 2010.
 346. Nerbonne JM , Kass RS . Molecular physiology of cardiac repolarization. Physiol Rev 85: 1205‐1253, 2005.
 347. Neyroud N , Tesson F , Denjoy I , Leibovici M , Donger C , Barhanin J , Faure S , Gary F , Coumel P , Petit C , Schwartz K , Guicheney P . A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange‐Nielsen cardioauditory syndrome. Nat Genet 15: 186‐189, 1997.
 348. Nguyen BL , Fishbein MC , Chen LS , Chen PS , Masroor S . Histopathological substrate for chronic atrial fibrillation in humans. Heart Rhythm 6: 454‐460, 2009.
 349. Nichols CG , Lopatin AN . Inward rectifier potassium channels. Annu Rev Physiol 59: 171‐191, 1997.
 350. Nichols CG , Makhina EN , Pearson WL , Sha Q , Lopatin AN . Inward rectification and implications for cardiac excitability. Circ Res 78: 1‐7, 1996.
 351. Nielsen JB , Bentzen BH , Olesen MS , David JP , Olesen SP , Haunso S , Svendsen JH , Schmitt N . Gain‐of‐function mutations in potassium channel subunit KCNE2 associated with early‐onset lone atrial fibrillation. Biomark Med 8: 557‐570, 2014.
 352. Nikmaram MR , Boyett MR , Kodama I , Suzuki R , Honjo H . Variation in effects of Cs+, UL‐FS‐49, and ZD‐7288 within sinoatrial node. Am J Physiol 272: H2782‐H2792, 1997.
 353. Nishisato K , Hashimoto A , Nakata T , Doi T , Yamamoto H , Nagahara D , Shimoshige S , Yuda S , Tsuchihashi K , Shimamoto K . Impaired cardiac sympathetic innervation and myocardial perfusion are related to lethal arrhythmia: Quantification of cardiac tracers in patients with ICDs. J Nucl Med 51: 1241‐1249, 2010.
 354. Niwa N , Nerbonne JM . Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation. J Mol Cell Cardiol 48: 12‐25, 2010.
 355. Nof E , Glikson M , Antzelevitch C . Genetics and sinus node dysfunction. J Atr Fibrillation 1: 328‐336, 2009.
 356. Nof E , Luria D , Brass D , Marek D , Lahat H , Reznik‐Wolf H , Pras E , Dascal N , Eldar M , Glikson M . Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. Circulation 116: 463‐470, 2007.
 357. Nuss HB , Houser SR . T‐type Ca2+ current is expressed in hypertrophied adult feline left ventricular myocytes. Circ Res 73: 777‐782, 1993.
 358. Nuss HB , Kaab S , Kass DA , Tomaselli GF , Marban E . Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure. Am J Physiol 277: H80‐H91, 1999.
 359. Nyegaard M , Overgaard MT , Sondergaard MT , Vranas M , Behr ER , Hildebrandt LL , Lund J , Hedley PL , Camm AJ , Wettrell G , Fosdal I , Christiansen M , Borglum AD . Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. Am J Hum Gen 91: 703‐712, 2012.
 360. O'Rourke B , Kass DA , Tomaselli GF , Kaab S , Tunin R , Marban E . Mechanisms of altered excitation‐contraction coupling in canine tachycardia‐induced heart failure, I: Experimental studies. Circ Res 84: 562‐570, 1999.
 361. Ohno S , Zankov DP , Ding WG , Itoh H , Makiyama T , Doi T , Shizuta S , Hattori T , Miyamoto A , Naiki N , Hancox JC , Matsuura H , Horie M . KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and idiopathic ventricular fibrillation. Circ Arrhythm Electrophysiol 4: 352‐361, 2011.
 362. Okada R , Kawai S . Histopathology of the conduction system in sudden cardiac death. Jpn Circ J 47: 573‐580, 1983.
 363. Olesen MS , Jespersen T , Nielsen JB , Liang B , Moller DV , Hedley P , Christiansen M , Varro A , Olesen SP , Haunso S , Schmitt N , Svendsen JH . Mutations in sodium channel beta‐subunit SCN3B are associated with early‐onset lone atrial fibrillation. Cardiovasc Res 89: 786‐793, 2011.
 364. Olson TM , Alekseev AE , Liu XK , Park S , Zingman LV , Bienengraeber M , Sattiraju S , Ballew JD , Jahangir A , Terzic A . Kv1.5 channelopathy due to KCNA5 loss‐of‐function mutation causes human atrial fibrillation. Hum Mol Genet 15: 2185‐2191, 2006.
 365. Olson TM , Alekseev AE , Moreau C , Liu XK , Zingman LV , Miki T , Seino S , Asirvatham SJ , Jahangir A , Terzic A . KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation. Nat Clin Pract Cardiovasc Med 4: 110‐116, 2007.
 366. Olson TM , Terzic A . Human K(ATP) channelopathies: Diseases of metabolic homeostasis. Pflugers Arch 460: 295‐306, 2010.
 367. Otway R , Vandenberg JI , Guo G , Varghese A , Castro ML , Liu J , Zhao J , Bursill JA , Wyse KR , Crotty H , Baddeley O , Walker B , Kuchar D , Thorburn C , Fatkin D . Stretch‐sensitive KCNQ1 mutation A link between genetic and environmental factors in the pathogenesis of atrial fibrillation? J Am Coll Cardiol 49: 578‐586, 2007.
 368. Ozgen N , Dun W , Sosunov EA , Anyukhovsky EP , Hirose M , Duffy HS , Boyden PA , Rosen MR . Early electrical remodeling in rabbit pulmonary vein results from trafficking of intracellular SK2 channels to membrane sites. Cardiovasc Res 75: 758‐769, 2007.
 369. Pandit SV , Berenfeld O , Anumonwo JM , Zaritski RM , Kneller J , Nattel S , Jalife J . Ionic determinants of functional reentry in a 2‐D model of human atrial cells during simulated chronic atrial fibrillation. Biophys J 88: 3806‐3821, 2005.
 370. Park DS , Fishman GI . The cardiac conduction system. Circulation 123: 904‐915, 2011.
 371. Patterson E , Lazzara R , Szabo B , Liu H , Tang D , Li YH , Scherlag BJ , Po SS . Sodium‐calcium exchange initiated by the Ca2+ transient: An arrhythmia trigger within pulmonary veins. J Am Coll Cardiol 47: 1196‐1206, 2006.
 372. Pereon Y , Demolombe S , Baro I , Drouin E , Charpentier F , Escande D . Differential expression of KvLQT1 isoforms across the human ventricular wall. Am J Physiol Heart Circ Physiol 278: H1908‐H1915, 2000.
 373. Perez‐Garcia MT , Kamp TJ , Marban E . Functional properties of cardiac L‐type calcium channels transiently expressed in HEK293 cells. Roles of alpha 1 and beta subunits. J Gen Physiol 105: 289‐305, 1995.
 374. Perez‐Reyes E . Molecular physiology of low‐voltage‐activated t‐type calcium channels. Physiol Rev 83: 117‐161, 2003.
 375. Perez‐Reyes E , Castellano A , Kim HS , Bertrand P , Baggstrom E , Lacerda AE , Wei XY , Birnbaumer L . Cloning and expression of a cardiac/brain beta subunit of the L‐type calcium channel. J Biol Chem 267: 1792‐1797, 1992.
 376. Persson F , Andersson B , Duker G , Jacobson I , Carlsson L . Functional effects of the late sodium current inhibition by AZD7009 and lidocaine in rabbit isolated atrial and ventricular tissue and Purkinje fibre. Eur J Pharmacol 558: 133‐143, 2007.
 377. Petrecca K , Amellal F , Laird DW , Cohen SA , Shrier A . Sodium channel distribution within the rabbit atrioventricular node as analysed by confocal microscopy. J Physiol 501(Pt 2): 263‐274, 1997.
 378. Piacentino V, III , Weber CR , Chen X , Weisser‐Thomas J , Margulies KB , Bers DM , Houser SR . Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 92: 651‐658, 2003.
 379. Pitt GS , Dun W , Boyden PA . Remodeled cardiac calcium channels. J Mol Cell Cardiol 41: 373‐388, 2006.
 380. Poelzing S , Akar FG , Baron E , Rosenbaum DS . Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall. Am J Physiol Heart Circ Physiol 286: H2001‐H2009, 2004.
 381. Pogwizd SM , Bers DM . Na/Ca exchange in heart failure: Contractile dysfunction and arrhythmogenesis. Ann N Y Acad Sci 976: 454‐465, 2002.
 382. Pogwizd SM , Qi M , Yuan W , Samarel AM , Bers DM . Upregulation of Na(+)/Ca(2+) exchanger expression and function in an arrhythmogenic rabbit model of heart failure. Circ Res 85: 1009‐1019, 1999.
 383. Pogwizd SM , Schlotthauer K , Li L , Yuan W , Bers DM . Arrhythmogenesis and contractile dysfunction in heart failure: Roles of sodium‐calcium exchange, inward rectifier potassium current, and residual beta‐adrenergic responsiveness. Circ Res 88: 1159‐1167, 2001.
 384. Pollack GH . Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart. J Physiol 255: 275‐298, 1976.
 385. Postma AV , Denjoy I , Hoorntje TM , Lupoglazoff J‐M , Da Costa A , Sebillon P , Mannens MMAM , Wilde AAM , Guicheney P . Absence of calsequestrin 2 causes severe forms of catecholaminergic polymorphic ventricular tachycardia. Circ Res 91: e21‐e26, 2002.
 386. Postma AV , Denjoy I , Kamblock J , Alders M , Lupoglazoff J‐M , Vaksmann G , Dubosq‐Bidot L , Sebillon P , Mannens MMAM , Guicheney P , Wilde AAM . Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients. J Med Genet 42: 863‐870, 2005.
 387. Prestle J , Dieterich S , Preuss M , Bieligk U , Hasenfuss G . Heterogeneous transmural gene expression of calcium‐handling proteins and natriuretic peptides in the failing human heart. Cardiovasc Res 43: 323‐331, 1999.
 388. Priori SG , Corr PB . Mechanisms underlying early and delayed afterdepolarizations induced by catecholamines. Am J Physiol 258: H1796‐H1805, 1990.
 389. Priori SG , Napolitano C , Tiso N , Memmi M , Vignati G , Bloise R , Sorrentino V , Danieli GA . Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 103: 196‐200, 2001.
 390. Priori SG , Pandit SV , Rivolta I , Berenfeld O , Ronchetti E , Dhamoon A , Napolitano C , Anumonwo J , di Barletta MR , Gudapakkam S , Bosi G , Stramba‐Badiale M , Jalife J . A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene. Circ Res 96: 800‐807, 2005.
 391. Probst V , Kyndt F , Potet F , Trochu J‐N , Mialet G , Demolombe S , Schott J‐J , Baró I , Escande D , Le Marec H . Haploinsufficiency in combination with aging causes SCN5A‐linked hereditary Lenègre disease. JAC 41: 643‐652, 2003.
 392. Prosser BL , Ward CW , Lederer WJ . X‐ROS signaling: Rapid mechano‐chemo transduction in heart. Science 333: 1440‐1445, 2011.
 393. Qi XY , Diness JG , Brundel BJ , Zhou XB , Naud P , Wu CT , Huang H , Harada M , Aflaki M , Dobrev D , Grunnet M , Nattel S . Role of small‐conductance calcium‐activated potassium channels in atrial electrophysiology and fibrillation in the dog. Circulation 129: 430‐440, 2014.
 394. Qu Y , Baroudi G , Yue Y , El‐Sherif N , Boutjdir M . Localization and modulation of {alpha}1D (Cav1.3) L‐type Ca channel by protein kinase A. Am J Physiol Heart Circ Physiol 288: H2123‐H2130, 2005.
 395. Ramakers C , Stengl M , Spatjens RL , Moorman AF , Vos MA . Molecular and electrical characterization of the canine cardiac ventricular septum. J Mol Cell Cardiol 38: 153‐161, 2005.
 396. Ramakers C , Vos MA , Doevendans PA , Schoenmakers M , Wu YS , Scicchitano S , Iodice A , Thomas GP , Antzelevitch C , Dumaine R . Coordinated down‐regulation of KCNQ1 and KCNE1 expression contributes to reduction of I(Ks) in canine hypertrophied hearts. Cardiovasc Res 57: 486‐496, 2003.
 397. Ravens U , Poulet C , Wettwer E , Knaut M . Atrial selectivity of antiarrhythmic drugs. J Physiol 591: 4087‐4097, 2013.
 398. Ravn LS , Aizawa Y , Pollevick GD , Hofman‐Bang J , Cordeiro JM , Dixen U , Jensen G , Wu Y , Burashnikov E , Haunso S , Guerchicoff A , Hu D , Svendsen JH , Christiansen M , Antzelevitch C . Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation. Heart Rhythm 5: 427‐435, 2008.
 399. Reinecke H , Studer R , Vetter R , Holtz J , Drexler H . Cardiac Na+/Ca2+ exchange activity in patients with end‐stage heart failure. Cardiovasc Res 31: 48‐54, 1996.
 400. Ritchie MD , Denny JC , Zuvich RL , Crawford DC , Schildcrout JS , Bastarache L , Ramirez AH , Mosley JD , Pulley JM , Basford MA , Bradford Y , Rasmussen LV , Pathak J , Chute CG , Kullo IJ , McCarty CA , Chisholm RL , Kho AN , Carlson CS , Larson EB , Jarvik GP , Sotoodehnia N , Cohorts for H, Aging Research in Genomic Epidemiology QRSG, Manolio TA , Li R , Masys DR , Haines JL , Roden DM . Genome‐ and phenome‐wide analyses of cardiac conduction identifies markers of arrhythmia risk. Circulation 127: 1377‐1385, 2013.
 401. Robinson RB , Boyden PA , Hoffman BF , Hewett KW . Electrical restitution process in dispersed canine cardiac Purkinje and ventricular cells. Am J Physiol 253: H1018‐H1025, 1987.
 402. Rook MB , Evers MM , Vos MA , Bierhuizen MF . Biology of cardiac sodium channel Nav1.5 expression. Cardiovasc Res 93: 12‐23, 2012.
 403. Rosati B , Grau F , McKinnon D . Regional variation in mRNA transcript abundance within the ventricular wall. J Mol Cell Cardiol 40: 295‐302, 2006.
 404. Rosati B , Pan Z , Lypen S , Wang HS , Cohen I , Dixon JE , McKinnon D . Regulation of KChIP2 potassium channel beta subunit gene expression underlies the gradient of transient outward current in canine and human ventricle. J Physiol 533: 119‐125, 2001.
 405. Rose J , Armoundas AA , Tian Y , DiSilvestre D , Burysek M , Halperin V , O'Rourke B , Kass DA , Marban E , Tomaselli GF . Molecular correlates of altered expression of potassium currents in failing rabbit myocardium. Am J Physiol Heart Circ Physiol 288: H2077‐H2087, 2005.
 406. Rosen MR , Nargeot J , Salama G . The case for the funny current and the calcium clock. Heart Rhythm 9: 616‐618, 2012.
 407. Roux‐Buisson N , Cacheux M , Fourest‐Lieuvin A , Fauconnier J , Brocard J , Denjoy I , Durand P , Guicheney P , Kyndt F , Leenhardt A , Le Marec H , Lucet V , Mabo P , Probst V , Monnier N , Ray PF , Santoni E , Tremeaux P , Lacampagne A , Faure J , Lunardi J , Marty I . Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human. Hum Mol Genet 21: 2759‐2767, 2012.
 408. Rozanski GJ , Xu Z , Whitney RT , Murakami H , Zucker IH . Electrophysiology of rabbit ventricular myocytes following sustained rapid ventricular pacing. J Mol Cell Cardiol 29: 721‐732, 1997.
 409. Ruan Y , Liu N , Priori SG . Sodium channel mutations and arrhythmias. Nat Rev Cardiol 6: 337‐348, 2009.
 410. Rubart M , Zipes DP . Mechanisms of sudden cardiac death. J Clin Invest 115: 2305‐2315, 2005.
 411. Rudy Y , Ackerman MJ , Bers DM , Clancy CE , Houser SR , London B , McCulloch AD , Przywara DA , Rasmusson RL , Solaro RJ , Trayanova NA , Van Wagoner DR , Varro A , Weiss JN , Lathrop DA . Systems approach to understanding electromechanical activity in the human heart: A national heart, lung, and blood institute workshop summary. Circulation 118: 1202‐1211, 2008.
 412. Saenen JB , Vrints CJ . Molecular aspects of the congenital and acquired long QT syndrome: Clinical implications. J Mol Cell Cardiol 44: 633‐646, 2008.
 413. Salata JJ , Jurkiewicz NK , Jow B , Folander K , Guinosso PJ, Jr. , Raynor B , Swanson R , Fermini B . IK of rabbit ventricle is composed of two currents: Evidence for IKs. Am J Physiol 271: H2477‐H2489, 1996.
 414. Sánchez‐Quintana D , Cabrera JA , Farré J , Climent V , Anderson RH , Ho SY . Sinus node revisited in the era of electroanatomical mapping and catheter ablation. Heart (British Cardiac Society) 91: 189‐194, 2005.
 415. Sanguinetti MC , Curran ME , Zou A , Shen J , Spector PS , Atkinson DL , Keating MT . Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 384: 80‐83, 1996.
 416. Sanguinetti MC , Jiang C , Curran ME , Keating MT . A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81: 299‐307, 1995.
 417. Sanguinetti MC , Jurkiewicz NK . Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 96: 195‐215, 1990.
 418. Sanguinetti MC , Zou A . Molecular physiology of cardiac delayed rectifier K+ channels. Heart Vessels(Suppl 12): 170‐172, 1997.
 419. Satin J , Kyle JW , Chen M , Bell P , Cribbs LL , Fozzard HA , Rogart RB . A mutant of TTX‐resistant cardiac sodium channels with TTX‐sensitive properties. Science 256: 1202‐1205, 1992.
 420. Schmitt N , Grunnet M , Olesen SP . Cardiac potassium channel subtypes: New roles in repolarization and arrhythmia. Physiol Rev 94: 609‐653, 2014.
 421. Schott JJ , Alshinawi C , Kyndt F , Probst V , Hoorntje TM , Hulsbeek M , Wilde AA , Escande D , Mannens MM , Le Marec H . Cardiac conduction defects associate with mutations in SCN5A. Nat Genet 23: 20‐21, 1999.
 422. Schott JJ , Charpentier F , Peltier S , Foley P , Drouin E , Bouhour JB , Donnelly P , Vergnaud G , Bachner L , Moisan JP , et al. Mapping of a gene for long QT syndrome to chromosome 4q25‐27. Am J Hum Gen 57: 1114‐1122, 1995.
 423. Schotten U , de Haan S , Verheule S , Harks EG , Frechen D , Bodewig E , Greiser M , Ram R , Maessen J , Kelm M , Allessie M , Van Wagoner DR . Blockade of atrial‐specific K+‐currents increases atrial but not ventricular contractility by enhancing reverse mode Na+/Ca2+‐exchange. Cardiovasc Res 73: 37‐47, 2007.
 424. Schotten U , Greiser M , Benke D , Buerkel K , Ehrenteidt B , Stellbrink C , Vazquez‐Jimenez JF , Schoendube F , Hanrath P , Allessie M . Atrial fibrillation‐induced atrial contractile dysfunction: A tachycardiomyopathy of a different sort. Cardiovasc Res 53: 192‐201, 2002.
 425. Schram G , Pourrier M , Melnyk P , Nattel S . Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res 90: 939‐950, 2002.
 426. Schram G , Pourrier M , Wang Z , White M , Nattel S . Barium block of Kir2 and human cardiac inward rectifier currents: Evidence for subunit‐heteromeric contribution to native currents. Cardiovasc Res 59: 328‐338, 2003.
 427. Schroder F , Handrock R , Beuckelmann DJ , Hirt S , Hullin R , Priebe L , Schwinger RH , Weil J , Herzig S . Increased availability and open probability of single L‐type calcium channels from failing compared with nonfailing human ventricle. Circulation 98: 969‐976, 1998.
 428. Schroeder BC , Waldegger S , Fehr S , Bleich M , Warth R , Greger R , Jentsch TJ . A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature 403: 196‐199, 2000.
 429. Schuessler RB . Abnormal sinus node function in clinical arrhythmias. J Cardiovasc Electrophysiol 14: 215‐217, 2003.
 430. Schulze‐Bahr E , Haverkamp W , Wedekind H , Rubie C , Hordt M , Borggrefe M , Assmann G , Breithardt G , Funke H . Autosomal recessive long‐QT syndrome (Jervell Lange‐Nielsen syndrome) is genetically heterogeneous. Hum Genet 100: 573‐576, 1997.
 431. Schulze‐Bahr E , Neu A , Friederich P , Kaupp UB , Breithardt G , Pongs O , Isbrandt D . Pacemaker channel dysfunction in a patient with sinus node disease. J Clin Invest 111: 1537‐1545, 2003.
 432. Schwartz PJ , Crotti L , Insolia R . Long‐QT syndrome: From genetics to management. Circ Arrhythm Electrophysiol 5: 868‐877, 2012.
 433. Schwinger RH , Bohm M , Schmidt U , Karczewski P , Bavendiek U , Flesch M , Krause EG , Erdmann E . Unchanged protein levels of SERCA II and phospholamban but reduced Ca2+ uptake and Ca(2+)‐ATPase activity of cardiac sarcoplasmic reticulum from dilated cardiomyopathy patients compared with patients with nonfailing hearts. Circulation 92: 3220‐3228, 1995.
 434. Schwinger RH , Hoischen S , Reuter H , Hullin R . Regional expression and functional characterization of the L‐type Ca2+‐channel in myocardium from patients with end‐stage heart failure and in non‐failing human hearts. J Mol Cell Cardiol 31: 283‐296, 1999.
 435. Schwinger RH , Munch G , Bolck B , Karczewski P , Krause EG , Erdmann E . Reduced Ca(2+)‐sensitivity of SERCA 2a in failing human myocardium due to reduced serin‐16 phospholamban phosphorylation. J Mol Cell Cardiol 31: 479‐491, 1999.
 436. Seino S , Miki T . Gene targeting approach to clarification of ion channel function: Studies of Kir6.x null mice. J Physiol 554: 295‐300, 2004.
 437. Selnick HG , Liverton NJ , Baldwin JJ , Butcher JW , Claremon DA , Elliott JM , Freidinger RM , King SA , Libby BE , McIntyre CJ , Pribush DA , Remy DC , Smith GR , Tebben AJ , Jurkiewicz NK , Lynch JJ , Salata JJ , Sanguinetti MC , Siegl PK , Slaughter DE , Vyas K . Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)‐2‐(2,4‐trifluoromethyl)‐N‐[2‐oxo‐5‐phenyl‐1‐(2,2,2‐trifluoroethyl)‐2,3‐dihydro‐1H‐benzo[e][1,4]diazepin‐3‐yl]acetamide. J Med Chem 40: 3865‐3868, 1997.
 438. Shah M , Akar FG , Tomaselli GF . Molecular basis of arrhythmias. Circulation 112: 2517‐2529, 2005.
 439. Shan J , Xie W , Betzenhauser M , Reiken S , Chen BX , Wronska A , Marks AR . Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res 111: 708‐717, 2012.
 440. Shang LL , Pfahnl AE , Sanyal S , Jiao Z , Allen J , Banach K , Fahrenbach J , Weiss D , Taylor WR , Zafari AM , Dudley SC, Jr . Human heart failure is associated with abnormal C‐terminal splicing variants in the cardiac sodium channel. Circ Res 101: 1146‐1154, 2007.
 441. Shannon TR , Pogwizd SM , Bers DM . Elevated sarcoplasmic reticulum Ca2+ leak in intact ventricular myocytes from rabbits in heart failure. Circ Res 93: 592‐594, 2003.
 442. Shi W , Wymore R , Yu H , Wu J , Wymore RT , Pan Z , Robinson RB , Dixon JE , McKinnon D , Cohen IS . Distribution and prevalence of hyperpolarization‐activated cation channel (HCN) mRNA expression in cardiac tissues. Circ Res 85: e1‐e6, 1999.
 443. Shibata EF , Drury T , Refsum H , Aldrete V , Giles W . Contributions of a transient outward current to repolarization in human atrium. Am J Physiol 257: H1773‐H1781, 1989.
 444. Shimoni Y , Clark RB , Giles WR . Role of an inwardly rectifying potassium current in rabbit ventricular action potential. J Physiol 448: 709‐727, 1992.
 445. Shiroshita‐Takeshita A , Sakabe M , Haugan K , Hennan JK , Nattel S . Model‐dependent effects of the gap junction conduction‐enhancing antiarrhythmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs. Circulation 115: 310‐318, 2007.
 446. Sicouri S , Antzelevitch C . A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Circ Res 68: 1729‐1741, 1991.
 447. Sigg DC. Cardiac Electrophysiology Methods and Models. New York: Springer, 2010.
 448. Silva J , Rudy Y . Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation 112: 1384‐1391, 2005.
 449. Skasa M , Jungling E , Picht E , Schondube F , Luckhoff A . L‐type calcium currents in atrial myocytes from patients with persistent and non‐persistent atrial fibrillation. Basic Res Cardiol 96: 151‐159, 2001.
 450. Smits JPP , Koopmann TT , Wilders R , Veldkamp MW , Opthof T , Bhuiyan ZA , Mannens MMAM , Balser JR , Tan HL , Bezzina CR , Wilde AAM . A mutation in the human cardiac sodium channel (E161K) contributes to sick sinus syndrome, conduction disease and Brugada syndrome in two families. J Mol Cell Cardiol 38: 969‐981, 2005.
 451. Soldatov NM . Genomic structure of human L‐type Ca2+ channel. Genomics 22: 77‐87, 1994.
 452. Soltysinska E , Olesen SP , Christ T , Wettwer E , Varro A , Grunnet M , Jespersen T . Transmural expression of ion channels and transporters in human nondiseased and end‐stage failing hearts. Pflugers Arch 459: 11‐23, 2009.
 453. Sossalla S , Kallmeyer B , Wagner S , Mazur M , Maurer U , Toischer K , Schmitto JD , Seipelt R , Schondube FA , Hasenfuss G , Belardinelli L , Maier LS . Altered Na+ currents in atrial fibrillation effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol 55: 2330‐2342, 2010.
 454. Spach MS , Lieberman M , Scott JG , Barr RC , Johnson EA , Kootsey JM . Excitation sequences of the atrial septum and the AV node in isolated hearts of the dog and rabbit. Circ Res 29: 156‐172, 1971.
 455. Splawski I , Timothy KW , Sharpe LM , Decher N , Kumar P , Bloise R , Napolitano C , Schwartz PJ , Joseph RM , Condouris K , Tager‐Flusberg H , Priori SG , Sanguinetti MC , Keating MT . Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119: 19‐31, 2004.
 456. Splawski I , Tristani‐Firouzi M , Lehmann MH , Sanguinetti MC , Keating MT . Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet 17: 338‐340, 1997.
 457. Stange M , Xu L , Balshaw D , Yamaguchi N , Meissner G . Characterization of recombinant skeletal muscle (Ser‐2843) and cardiac muscle (Ser‐2809) ryanodine receptor phosphorylation mutants. J Biol Chem 278: 51693‐51702, 2003.
 458. Stevenson WG , Stevenson LW , Middlekauff HR , Saxon LA . Sudden death prevention in patients with advanced ventricular dysfunction. Circulation 88: 2953‐2961, 1993.
 459. Studer R , Reinecke H , Bilger J , Eschenhagen T , Bohm M , Hasenfuss G , Just H , Holtz J , Drexler H . Gene expression of the cardiac Na(+)‐Ca2+ exchanger in end‐stage human heart failure. Circ Res 75: 443‐453, 1994.
 460. Sugai M , Kono R , Kunita Y . A morphologic study on human conduction system of heart considering influences of some disorders of individuals. Acta Pathol Jpn 31: 13‐25, 1981.
 461. Sun Y , Yang YQ , Gong XQ , Wang XH , Li RG , Tan HW , Liu X , Fang WY , Bai D . Novel germline GJA5/connexin40 mutations associated with lone atrial fibrillation impair gap junctional intercellular communication. Hum Mutat 34: 603‐609, 2013.
 462. Suzuki M , Li RA , Miki T , Uemura H , Sakamoto N , Ohmoto‐Sekine Y , Tamagawa M , Ogura T , Seino S , Marban E , Nakaya H . Functional roles of cardiac and vascular ATP‐sensitive potassium channels clarified by Kir6.2‐knockout mice. Circ Res 88: 570‐577, 2001.
 463. Suzuki M , Sasaki N , Miki T , Sakamoto N , Ohmoto‐Sekine Y , Tamagawa M , Seino S , Marban E , Nakaya H . Role of sarcolemmal K(ATP) channels in cardioprotection against ischemia/reperfusion injury in mice. J Clin Invest 109: 509‐516, 2002.
 464. Swaminathan PD , Purohit A , Soni S , Voigt N , Singh MV , Glukhov AV , Gao Z , He BJ , Luczak ED , Joiner M‐lA , Kutschke W , Yang J , Donahue JK , Weiss RM , Grumbach IM , Ogawa M , Chen P‐S , Efimov I , Dobrev D , Mohler PJ , Hund TJ , Anderson ME . Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J Clin Invest 121: 3277‐3288, 2011.
 465. Szabo G , Szentandrassy N , Biro T , Toth BI , Czifra G , Magyar J , Banyasz T , Varro A , Kovacs L , Nanasi PP . Asymmetrical distribution of ion channels in canine and human left‐ventricular wall: Epicardium versus midmyocardium. Pflugers Arch 450: 307‐316, 2005.
 466. Szentadrassy N , Banyasz T , Biro T , Szabo G , Toth BI , Magyar J , Lazar J , Varro A , Kovacs L , Nanasi PP . Apico‐basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium. Cardiovasc Res 65: 851‐860, 2005.
 467. Szumowski L , Sanders P , Walczak F , Hocini M , Jaïs P , Kepski R , Szufladowicz E , Urbanek P , Derejko P , Bodalski R , Haïssaguerre M . Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction. JAC 44: 1700‐1706, 2004.
 468. Takahashi N , Morishige K , Jahangir A , Yamada M , Findlay I , Koyama H , Kurachi Y . Molecular cloning and functional expression of cDNA encoding a second class of inward rectifier potassium channels in the mouse brain. J Biol Chem 269: 23274‐23279, 1994.
 469. Tan AY , Li H , Wachsmann‐Hogiu S , Chen LS , Chen PS , Fishbein MC . Autonomic innervation and segmental muscular disconnections at the human pulmonary vein‐atrial junction: Implications for catheter ablation of atrial‐pulmonary vein junction. J Am Coll Cardiol 48: 132‐143, 2006.
 470. Tawil R , Ptacek LJ , Pavlakis SG , DeVivo DC , Penn AS , Ozdemir C , Griggs RC . Andersen's syndrome: Potassium‐sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol 35: 326‐330, 1994.
 471. Tellez JO , Dobrzynski H , Greener ID , Graham GM , Laing E , Honjo H , Hubbard SJ , Boyett MR , Billeter R . Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit. Circ Res 99: 1384‐1393, 2006.
 472. Tellez JO , Mczewski M , Yanni J , Sutyagin P , Mackiewicz U , Atkinson A , Inada S , Beresewicz A , Billeter R , Dobrzynski H , Boyett MR . Ageing‐dependent remodelling of ion channel and Ca2+ clock genes underlying sino‐atrial node pacemaking. Exp Physiol 96: 1163‐1178, 2011.
 473. Templin C , Ghadri JR , Rougier JS , Baumer A , Kaplan V , Albesa M , Sticht H , Rauch A , Puleo C , Hu D , Barajas‐Martinez H , Antzelevitch C , Luscher TF , Abriel H , Duru F . Identification of a novel loss‐of‐function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J 32: 1077‐1088, 2011.
 474. Terentyev D , Gyorke I , Belevych AE , Terentyeva R , Sridhar A , Nishijima Y , de Blanco EC , Khanna S , Sen CK , Cardounel AJ , Carnes CA , Gyorke S . Redox modification of ryanodine receptors contributes to sarcoplasmic reticulum Ca2+ leak in chronic heart failure. Circ Res 103: 1466‐1472, 2008.
 475. Tessier S , Karczewski P , Krause EG , Pansard Y , Acar C , Lang‐Lazdunski M , Mercadier JJ , Hatem SN . Regulation of the transient outward K+ current by Ca2+/calmodulin‐dependent protein kinases II in human atrial myocytes. Circ Res 85: 810‐819, 1999.
 476. Tester DJ , Arya P , Will M , Haglund CM , Farley AL , Makielski JC , Ackerman MJ . Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing. Heart Rhythm 3: 800‐805, 2006.
 477. Thomas SA , Schuessler RB , Berul CI , Beardslee MA , Beyer EC , Mendelsohn ME , Saffitz JE . Disparate effects of deficient expression of connexin43 on atrial and ventricular conduction: Evidence for chamber‐specific molecular determinants of conduction. Circulation 97: 686‐691, 1998.
 478. Tinel N , Diochot S , Borsotto M , Lazdunski M , Barhanin J . KCNE2 confers background current characteristics to the cardiac KCNQ1 potassium channel. Embo J 19: 6326‐6330, 2000.
 479. Tomaselli GF , Beuckelmann DJ , Calkins HG , Berger RD , Kessler PD , Lawrence JH , Kass D , Feldman AM , Marban E . Sudden cardiac death in heart failure. The role of abnormal repolarization. Circulation 90: 2534‐2539, 1994.
 480. Tranum‐Jensen J , Wilde AA , Vermeulen JT , Janse MJ . Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts. Circ Res 69: 429‐437, 1991.
 481. Trautwein W , Kassebaum DG . On the mechanism of spontaneous impulse generation in the pacemaker of the heart. J Gen Physiol 45: 317‐330, 1961.
 482. Tristani‐Firouzi M , Jensen JL , Donaldson MR , Sansone V , Meola G , Hahn A , Bendahhou S , Kwiecinski H , Fidzianska A , Plaster N , Fu YH , Ptacek LJ , Tawil R . Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 110: 381‐388, 2002.
 483. Tristani‐Firouzi M , Sanguinetti MC . Structural determinants and biophysical properties of HERG and KCNQ1 channel gating. J Mol Cell Cardiol 35: 27‐35, 2003.
 484. Tseng GN , Hoffman BF . Two components of transient outward current in canine ventricular myocytes. Circ Res 64: 633‐647, 1989.
 485. Tsuji Y , Opthof T , Kamiya K , Yasui K , Liu W , Lu Z , Kodama I . Pacing‐induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle. Cardiovasc Res 48: 300‐309, 2000.
 486. Tsuji Y , Zicha S , Qi XY , Kodama I , Nattel S . Potassium channel subunit remodeling in rabbits exposed to long‐term bradycardia or tachycardia: Discrete arrhythmogenic consequences related to differential delayed‐rectifier changes. Circulation 113: 345‐355, 2006.
 487. Tuomi JM , Tyml K , Jones DL . Atrial tachycardia/fibrillation in the connexin 43 G60S mutant (Oculodentodigital dysplasia) mouse. Am J Physiol Heart Circ Physiol 300: H1402‐H1411, 2011.
 488. Tuteja D , Xu D , Timofeyev V , Lu L , Sharma D , Zhang Z , Xu Y , Nie L , Vazquez AE , Young JN , Glatter KA , Chiamvimonvat N . Differential expression of small‐conductance Ca2+‐activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes. Am J Physiol Heart Circ Physiol 289: H2714‐H2723, 2005.
 489. Ueda K , Hirano Y , Higashiuesato Y , Aizawa Y , Hayashi T , Inagaki N , Tana T , Ohya Y , Takishita S , Muratani H , Hiraoka M , Kimura A . Role of HCN4 channel in preventing ventricular arrhythmia. J Hum Genet 54: 115‐121, 2009.
 490. Ueda K , Nakamura K , Hayashi T , Inagaki N , Takahashi M , Arimura T , Morita H , Higashiuesato Y , Hirano Y , Yasunami M , Takishita S , Yamashina A , Ohe T , Sunamori M , Hiraoka M , Kimura A . Functional characterization of a trafficking‐defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem 279: 27194‐27198, 2004.
 491. Ueda K , Valdivia C , Medeiros‐Domingo A , Tester DJ , Vatta M , Farrugia G , Ackerman MJ , Makielski JC . Syntrophin mutation associated with long QT syndrome through activation of the nNOS‐SCN5A macromolecular complex. Proc Natl Acad Sci U S A 105: 9355‐9360, 2008.
 492. Ufret‐Vincenty CA , Baro DJ , Lederer WJ , Rockman HA , Quinones LE , Santana LF . Role of sodium channel deglycosylation in the genesis of cardiac arrhythmias in heart failure. J Biol Chem 276: 28197‐28203, 2001.
 493. Undrovinas AI , Maltsev VA , Kyle JW , Silverman N , Sabbah HN . Gating of the late Na+ channel in normal and failing human myocardium. J Mol Cell Cardiol 34: 1477‐1489, 2002.
 494. Undrovinas AI , Maltsev VA , Sabbah HN . Repolarization abnormalities in cardiomyocytes of dogs with chronic heart failure: Role of sustained inward current. Cell Mol Life Sci 55: 494‐505, 1999.
 495. Vaidya D , Tamaddon HS , Lo CW , Taffet SM , Delmar M , Morley GE , Jalife J . Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development. Circ Res 88: 1196‐1202, 2001.
 496. Vaitkevicius R , Saburkina I , Rysevaite K , Vaitkeviciene I , Pauziene N , Zaliunas R , Schauerte P , Jalife J , Pauza DH . Nerve supply of the human pulmonary veins: An anatomical study. Heart Rhythm 6: 221‐228, 2009.
 497. Valdivia CR , Chu WW , Pu J , Foell JD , Haworth RA , Wolff MR , Kamp TJ , Makielski JC . Increased late sodium current in myocytes from a canine heart failure model and from failing human heart. J Mol Cell Cardiol 38: 475‐483, 2005.
 498. Valdivia HH , Kaplan JH , Ellis‐Davies GC , Lederer WJ . Rapid adaptation of cardiac ryanodine receptors: Modulation by Mg2+ and phosphorylation. Science 267: 1997‐2000, 1995.
 499. van Rijen HV , Eckardt D , Degen J , Theis M , Ott T , Willecke K , Jongsma HJ , Opthof T , de Bakker JM . Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation 109: 1048‐1055, 2004.
 500. van Veen TA , Stein M , Royer A , Le Quang K , Charpentier F , Colledge WH , Huang CL , Wilders R , Grace AA , Escande D , de Bakker JM , van Rijen HV . Impaired impulse propagation in Scn5a‐knockout mice: Combined contribution of excitability, connexin expression, and tissue architecture in relation to aging. Circulation 112: 1927‐1935, 2005.
 501. Van Wagoner DR , Nerbonne JM . Molecular basis of electrical remodeling in atrial fibrillation. J Mol Cell Cardiol 32: 1101‐1117, 2000.
 502. Van Wagoner DR , Pond AL , Lamorgese M , Rossie SS , McCarthy PM , Nerbonne JM . Atrial L‐Type Ca2+ Currents and Human Atrial Fibrillation. Circ Res 85: 428‐436, 1999.
 503. Van Wagoner DR , Pond AL , McCarthy PM , Trimmer JS , Nerbonne JM . Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ Res 80: 772‐781, 1997.
 504. Varro A , Balati B , Iost N , Takacs J , Virag L , Lathrop DA , Csaba L , Talosi L , Papp JG . The role of the delayed rectifier component IKs in dog ventricular muscle and Purkinje fibre repolarization. J Physiol 523(Pt 1): 67‐81, 2000.
 505. Varro A , Nanasi PP , Lathrop DA . Potassium currents in isolated human atrial and ventricular cardiocytes. Acta Physiol Scand 149: 133‐142, 1993.
 506. Vatta M , Ackerman MJ , Ye B , Makielski JC , Ughanze EE , Taylor EW , Tester DJ , Balijepalli RC , Foell JD , Li Z , Kamp TJ , Towbin JA . Mutant caveolin‐3 induces persistent late sodium current and is associated with long‐QT syndrome. Circulation 114: 2104‐2112, 2006.
 507. Veldkamp MW , van Ginneken AC , Bouman LN . Single delayed rectifier channels in the membrane of rabbit ventricular myocytes. Circ Res 72: 865‐878, 1993.
 508. Verheijck EE , Wessels A , van Ginneken AC , Bourier J , Markman MW , Vermeulen JL , de Bakker JM , Lamers WH , Opthof T , Bouman LN . Distribution of atrial and nodal cells within the rabbit sinoatrial node: Models of sinoatrial transition. Circulation 97: 1623‐1631, 1998.
 509. Verheule S , van Kempen MJ , te Welscher PH , Kwak BR , Jongsma HJ . Characterization of gap junction channels in adult rabbit atrial and ventricular myocardium. Circ Res 80: 673‐681, 1997.
 510. Verkerk AO , Wilders R , Coronel R , Ravesloot JH , Verheijck EE . Ionic remodeling of sinoatrial node cells by heart failure. Circulation 108: 760‐766, 2003.
 511. Vest JA , Wehrens XHT , Reiken SR , Lehnart SE , Dobrev D , Chandra P , Danilo P , Ravens U , Rosen MR , Marks AR . Defective cardiac ryanodine receptor regulation during atrial fibrillation. Circulation 111: 2025‐2032, 2005.
 512. Vinogradova TM , Lyashkov AE , Zhu W , Ruknudin AM , Sirenko S , Yang D , Deo S , Barlow M , Johnson S , Caffrey JL , Zhou Y‐Y , Xiao R‐P , Cheng H , Stern MD , Maltsev VA , Lakatta EG . High basal protein kinase A‐dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells. Circ Res 98: 505‐514, 2006.
 513. Virag L , Iost N , Opincariu M , Szolnoky J , Szecsi J , Bogats G , Szenohradszky P , Varro A , Papp JG . The slow component of the delayed rectifier potassium current in undiseased human ventricular myocytes. Cardiovasc Res 49: 790‐797, 2001.
 514. Voigt N , Trafford AW , Ravens U , Dobrev D . Abstract 2630: Cellular and molecular determinants of altered atrial Ca2+ signaling in patients with chronic atrial fibrillation. Circulation 120: S667‐d‐668, 2009.
 515. Voigt N , Trafford AW , Wang Q , Wehrens XH , Ravens U , Dobrev D . Abstract 16909: Sarcoplasmic reticulum calcium leak and enhanced NCX increase occurrence of delayed afterdepolarisations in atrial myocytes from patients with chronic atrial fibrillation. Circulation 122: A16909, 2010.
 516. Voigt N , Trausch A , Knaut M , Matschke K , Varro A , Van Wagoner DR , Nattel S , Ravens U , Dobrev D . Left‐to‐right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation. Circ Arrhythm Electrophysiol 3: 472‐480, 2010.
 517. Volders PG , Sipido KR , Carmeliet E , Spatjens RL , Wellens HJ , Vos MA . Repolarizing K+ currents ITO1 and IKs are larger in right than left canine ventricular midmyocardium. Circulation 99: 206‐210, 1999.
 518. Volders PG , Stengl M , van Opstal JM , Gerlach U , Spatjens RL , Beekman JD , Sipido KR , Vos MA . Probing the contribution of IKs to canine ventricular repolarization: Key role for beta‐adrenergic receptor stimulation. Circulation 107: 2753‐2760, 2003.
 519. Vozzi C , Dupont E , Coppen SR , Yeh HI , Severs NJ . Chamber‐related differences in connexin expression in the human heart. J Mol Cell Cardiol 31: 991‐1003, 1999.
 520. Wagner S , Dybkova N , Rasenack EC , Jacobshagen C , Fabritz L , Kirchhof P , Maier SK , Zhang T , Hasenfuss G , Brown JH , Bers DM , Maier LS . Ca2+/calmodulin‐dependent protein kinase II regulates cardiac Na+ channels. J Clin Invest 116: 3127‐3138, 2006.
 521. Wagner S , Hacker E , Grandi E , Weber SL , Dybkova N , Sossalla S , Sowa T , Fabritz L , Kirchhof P , Bers DM , Maier LS . Ca/calmodulin kinase II differentially modulates potassium currents. Circ Arrhythm Electrophysiol 2: 285‐294, 2009.
 522. Wagner S , Ruff HM , Weber SL , Bellmann S , Sowa T , Schulte T , Grandi E , Bers DM , Backs J , Belardinelli L , Maier LS . Reactive oxygen species‐activated Ca/calmodulin kinase II{delta} is required for late INa augmentation leading to cellular Na and Ca overload. Circ Res 108: 555‐565, 2011.
 523. Wainger BJ , DeGennaro M , Santoro B , Siegelbaum SA , Tibbs GR . Molecular mechanism of cAMP modulation of HCN pacemaker channels. Nature 411: 805‐810, 2001.
 524. Wakili R , Voigt N , Kaab S , Dobrev D , Nattel S . Recent advances in the molecular pathophysiology of atrial fibrillation. J Clin Invest 121: 2955‐2968, 2011.
 525. Walsh KB , Kass RS . Regulation of a heart potassium channel by protein kinase A and C. Science 242: 67‐69, 1988.
 526. Walsh KB , Kass RS . Distinct voltage‐dependent regulation of a heart‐delayed IK by protein kinases A and C. Am J Physiol 261: C1081‐C1090, 1991.
 527. Wang DW , Viswanathan PC , Balser JR , George AL , Benson DW . Clinical, genetic, and biophysical characterization of SCN5A mutations associated with atrioventricular conduction block. Circulation 105: 341‐346, 2002.
 528. Wang HS , Cohen IS . Calcium channel heterogeneity in canine left ventricular myocytes. J Physiol 547: 825‐833, 2003.
 529. Wang J , Schwinger RH , Frank K , Muller‐Ehmsen J , Martin‐Vasallo P , Pressley TA , Xiang A , Erdmann E , McDonough AA . Regional expression of sodium pump subunits isoforms and Na+‐Ca++ exchanger in the human heart. J Clin Invest 98: 1650‐1658, 1996.
 530. Wang Q , Curran ME , Splawski I , Burn TC , Millholland JM , VanRaay TJ , Shen J , Timothy KW , Vincent GM , de Jager T , Schwartz PJ , Toubin JA , Moss AJ , Atkinson DL , Landes GM , Connors TD , Keating MT . Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 12: 17‐23, 1996.
 531. Wang Q , Li Z , Shen J , Keating MT . Genomic organization of the human SCN5A gene encoding the cardiac sodium channel. Genomics 34: 9‐16, 1996.
 532. Wang Q , Shen J , Splawski I , Atkinson D , Li Z , Robinson JL , Moss AJ , Towbin JA , Keating MT . SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 80: 805‐811, 1995.
 533. Wang Z , Fermini B , Nattel S . Delayed rectifier outward current and repolarization in human atrial myocytes. Circ Res 73: 276‐285, 1993.
 534. Wang Z , Fermini B , Nattel S . Sustained depolarization‐induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ Res 73: 1061‐1076, 1993.
 535. Wang Z , Yue L , White M , Pelletier G , Nattel S . Differential distribution of inward rectifier potassium channel transcripts in human atrium versus ventricle. Circulation 98: 2422‐2428, 1998.
 536. Wang ZG , Pelletier LC , Talajic M , Nattel S . Effects of flecainide and quinidine on human atrial action potentials. Role of rate‐dependence and comparison with guinea pig, rabbit, and dog tissues. Circulation 82: 274‐283, 1990.
 537. Watanabe E , Yasui K , Kamiya K , Yamaguchi T , Sakuma I , Honjo H , Ozaki Y , Morimoto S , Hishida H , Kodama I . Upregulation of KCNE1 induces QT interval prolongation in patients with chronic heart failure. Circ J 71: 471‐478, 2007.
 538. Watanabe H , Darbar D , Kaiser DW , Jiramongkolchai K , Chopra S , Donahue BS , Kannankeril PJ , Roden DM . Mutations in sodium channel beta1‐ and beta2‐subunits associated with atrial fibrillation. Circ Arrhythm Electrophysiol 2: 268‐275, 2009.
 539. Watanabe H , Koopmann TT , Le Scouarnec S , Yang T , Ingram CR , Schott JJ , Demolombe S , Probst V , Anselme F , Escande D , Wiesfeld AC , Pfeufer A , Kaab S , Wichmann HE , Hasdemir C , Aizawa Y , Wilde AA , Roden DM , Bezzina CR . Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest 118: 2260‐2268, 2008.
 540. Watanabe T , Delbridge LM , Bustamante JO , McDonald TF . Heterogeneity of the action potential in isolated rat ventricular myocytes and tissue. Circ Res 52: 280‐290, 1983.
 541. Weber MA , Gunther M , Lichy MP , Delorme S , Bongers A , Thilmann C , Essig M , Zuna I , Schad LR , Debus J , Schlemmer HP . Comparison of arterial spin‐labeling techniques and dynamic susceptibility‐weighted contrast‐enhanced MRI in perfusion imaging of normal brain tissue. Invest Radiol 38: 712‐718, 2003.
 542. Wettwer E , Amos G , Gath J , Zerkowski HR , Reidemeister JC , Ravens U . Transient outward current in human and rat ventricular myocytes. Cardiovasc Res 27: 1662‐1669, 1993.
 543. Wettwer E , Amos GJ , Posival H , Ravens U . Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin. Circ Res 75: 473‐482, 1994.
 544. Wettwer E , Hala O , Christ T , Heubach JF , Dobrev D , Knaut M , Varro A , Ravens U . Role of IKur in controlling action potential shape and contractility in the human atrium: Influence of chronic atrial fibrillation. Circulation 110: 2299‐2306, 2004.
 545. Wetzel GT , Chen F , Klitzner TS . L‐ and T‐type calcium channels in acutely isolated neonatal and adult cardiac myocytes. Pediatr Res 30: 89‐94, 1991.
 546. Wetzel GT , Chen F , Klitzner TS . Ca2+ channel kinetics in acutely isolated fetal, neonatal, and adult rabbit cardiac myocytes. Circ Res 72: 1065‐1074, 1993.
 547. Wickenden AD , Jegla TJ , Kaprielian R , Backx PH . Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle. Am J Physiol 276: H1599‐H1607, 1999.
 548. Wilders R , Kumar R , Joyner RW , Jongsma HJ , Verheijck EE , Golod D , van Ginneken AC , Goolsby WN . Action potential conduction between a ventricular cell model and an isolated ventricular cell. Biophys J 70: 281‐295, 1996.
 549. Wirka RC , Gore S , Van Wagoner DR , Arking DE , Lubitz SA , Lunetta KL , Benjamin EJ , Alonso A , Ellinor PT , Barnard J , Chung MK , Smith JD . A common connexin‐40 gene promoter variant affects connexin‐40 expression in human atria and is associated with atrial fibrillation. Circ Arrhythm Electrophysiol 4: 87‐93, 2011.
 550. Workman AJ , Kane KA , Rankin AC . Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation. Cardiovasc Res 59: 593‐602, 2003.
 551. Workman AJ , Kane KA , Rankin AC . Cellular bases for human atrial fibrillation. Heart Rhythm 5: S1‐S6, 2008.
 552. Workman AJ , Kane KA , Rankin AC . The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation. Cardiovasc Res 52: 226‐235, 2001.
 553. Wu G , Huang CX , Tang YH , Jiang H , Wan J , Chen H , Xie Q , Huang ZR . Changes of IK,ATP current density and allosteric modulation during chronic atrial fibrillation. Chin Med J (Engl) 118: 1161‐1166, 2005.
 554. Wu Y , Gao Z , Chen B , Koval OM , Singh MV , Guan X , Hund TJ , Kutschke W , Sarma S , Grumbach IM , Wehrens XHT , Mohler PJ , Song L‐S , Anderson ME . Calmodulin kinase II is required for fight or flight sinoatrial node physiology. Proc Natl Acad Sci U S A 106: 5972‐5977, 2009.
 555. Xia M , Jin Q , Bendahhou S , He Y , Larroque MM , Chen Y , Zhou Q , Yang Y , Liu Y , Liu B , Zhu Q , Zhou Y , Lin J , Liang B , Li L , Dong X , Pan Z , Wang R , Wan H , Qiu W , Xu W , Eurlings P , Barhanin J , Chen Y . A Kir2.1 gain‐of‐function mutation underlies familial atrial fibrillation. Biochem Biophy Res Comm 332: 1012‐1019, 2005.
 556. Xiao B , Sutherland C , Walsh MP , Chen SR . Protein kinase A phosphorylation at serine‐2808 of the cardiac Ca2+‐release channel (ryanodine receptor) does not dissociate 12.6‐kDa FK506‐binding protein (FKBP12.6). Circ Res 94: 487‐495, 2004.
 557. Xiao L , Coutu P , Villeneuve LR , Tadevosyan A , Maguy A , Le Bouter S , Allen BG , Nattel S . Mechanisms underlying rate‐dependent remodeling of transient outward potassium current in canine ventricular myocytes. Circ Res 103: 733‐742, 2008.
 558. Xiong W , Tian Y , DiSilvestre D , Tomaselli GF . Transmural heterogeneity of Na+‐Ca2+ exchange: Evidence for differential expression in normal and failing hearts. Circ Res 97: 207‐209, 2005.
 559. Xu H , Dixon JE , Barry DM , Trimmer JS , Merlie JP , McKinnon D , Nerbonne JM . Developmental analysis reveals mismatches in the expression of K+ channel alpha subunits and voltage‐gated K+ channel currents in rat ventricular myocytes. J Gen Physiol 108: 405‐419, 1996.
 560. Xu H , Guo W , Nerbonne JM . Four kinetically distinct depolarization‐activated K+ currents in adult mouse ventricular myocytes. J Gen Physiol 113: 661‐678, 1999.
 561. Xu Y , Tuteja D , Zhang Z , Xu D , Zhang Y , Rodriguez J , Nie L , Tuxson HR , Young JN , Glatter KA , Vazquez AE , Yamoah EN , Chiamvimonvat N . Molecular identification and functional roles of a Ca(2+)‐activated K+ channel in human and mouse hearts. J Biol Chem 278: 49085‐49094, 2003.
 562. Yamada KA , Kanter EM , Green KG , Saffitz JE . Transmural distribution of connexins in rodent hearts. J Cardiovasc Electrophysiol 15: 710‐715, 2004.
 563. Yamada S , Kane GC , Behfar A , Liu XK , Dyer RB , Faustino RS , Miki T , Seino S , Terzic A . Protection conferred by myocardial ATP‐sensitive K+ channels in pressure overload‐induced congestive heart failure revealed in KCNJ11 Kir6.2‐null mutant. J Physiol 577: 1053‐1065, 2006.
 564. Yan GX , Antzelevitch C . Cellular basis for the normal T wave and the electrocardiographic manifestations of the long‐QT syndrome. Circulation 98: 1928‐1936, 1998.
 565. Yan GX , Shimizu W , Antzelevitch C . Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations. Circulation 98: 1921‐1927, 1998.
 566. Yang Y , Chen X , Margulies K , Jeevanandam V , Pollack P , Bailey BA , Houser SR . L‐type Ca2+ channel alpha 1c subunit isoform switching in failing human ventricular myocardium. J Mol Cell Cardiol 32: 973‐984, 2000.
 567. Yang Y , Li J , Lin X , Yang Y , Hong K , Wang L , Liu J , Li L , Yan D , Liang D , Xiao J , Jin H , Wu J , Zhang Y , Chen YH . Novel KCNA5 loss‐of‐function mutations responsible for atrial fibrillation. J Hum Genet 54: 277‐283, 2009.
 568. Yang Y , Liang B , Liu J , Li J , Grunnet M , Olesen SP , Rasmussen HB , Ellinor PT , Gao L , Lin X , Li L , Wang L , Xiao J , Liu Y , Zhang S , Liang D , Peng L , Jespersen T , Chen YH . Identification of a Kir3.4 mutation in congenital long QT syndrome. Am J Hum Gen 86: 872‐880, 2010.
 569. Yang Y , Xia M , Jin Q , Bendahhou S , Shi J , Chen Y , Liang B , Lin J , Liu Y , Liu B , Zhou Q , Zhang D , Wang R , Ma N , Su X , Niu K , Pei Y , Xu W , Chen Z , Wan H , Cui J , Barhanin J , Chen Y . Identification of a KCNE2 gain‐of‐function mutation in patients with familial atrial fibrillation. Am J Hum Gen 75: 899‐905, 2004.
 570. Yaniv Y , Maltsev VA . Numerical modeling calcium and CaMKII effects in the SA node. Front Pharmacol 5: 58, 2014.
 571. Yanni J , Maczewski M , Mackiewicz U , Siew S , Fedorenko O , Atkinson A , Price M , Beresewicz A , Anderson RH , Boyett MR , Dobrzynski H . Structural and functional alterations in the atrioventricular node and atrioventricular ring tissue in ischaemia‐induced heart failure. Histol Histopathol 297: 891‐902, 2014.
 572. Yanni J , Tellez JO , Maczewski M , Mackiewicz U , Beresewicz A , Billeter R , Dobrzynski H , Boyett MR . Changes in ion channel gene expression underlying heart failure‐induced sinoatrial node dysfunction. Circ Heart Fail 4: 496‐508, 2011.
 573. Yanni J , Tellez JO , Sutyagin PV , Boyett MR , Dobrzynski H . Structural remodelling of the sinoatrial node in obese old rats. J Mol Cell Cardiol 48: 653‐662, 2010.
 574. Yao JA , Gutstein DE , Liu F , Fishman GI , Wit AL . Cell coupling between ventricular myocyte pairs from connexin43‐deficient murine hearts. Circ Res 93: 736‐743, 2003.
 575. Yoo S , Dobrzynski H , Fedorov VV , Xu S‐Z , Yamanushi TT , Jones SA , Yamamoto M , Nikolski VP , Efimov IR , Boyett MR . Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat. Circulation 114: 1360‐1371, 2006.
 576. Yu FH , Catterall WA . Overview of the voltage‐gated sodium channel family. Genome Biol 4: 207, 2003.
 577. Yuan W , Bers DM . Ca‐dependent facilitation of cardiac Ca current is due to Ca‐calmodulin‐dependent protein kinase. Am J Physiol 267: H982‐H993, 1994.
 578. Yue L , Wang Z , Rindt H , Nattel S . Molecular evidence for a role of Shaw (Kv3) potassium channel subunits in potassium currents of dog atrium. J Physiol 527(Pt 3): 467‐478, 2000.
 579. Zaritsky JJ , Eckman DM , Wellman GC , Nelson MT , Schwarz TL . Targeted disruption of Kir2.1 and Kir2.2 genes reveals the essential role of the inwardly rectifying K(+) current in K(+)‐mediated vasodilation. Circ Res 87: 160‐166, 2000.
 580. Zaritsky JJ , Redell JB , Tempel BL , Schwarz TL . The consequences of disrupting cardiac inwardly rectifying K(+) current (I(K1)) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes. J Physiol 533: 697‐710, 2001.
 581. Zhang H , Flagg TP , Nichols CG . Cardiac sarcolemmal K(ATP) channels: Latest twists in a questing tale! J Mol Cell Cardiol 48: 71‐75, 2009.
 582. Zhang L , Benson DW , Tristani‐Firouzi M , Ptacek LJ , Tawil R , Schwartz PJ , George AL , Horie M , Andelfinger G , Snow GL , Fu Y‐H , Ackerman MJ , Vincent GM . Electrocardiographic features in Andersen‐Tawil syndrome patients with KCNJ2 mutations: Characteristic T‐U‐wave patterns predict the KCNJ2 genotype. Circulation 111: 2720‐2726, 2005.
 583. Zhang T , Maier LS , Dalton ND , Miyamoto S , Ross J, Jr. , Bers DM , Brown JH . The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure. Circ Res 92: 912‐919, 2003.
 584. Zhang X , Chen S , Yoo S , Chakrabarti S , Zhang T , Ke T , Oberti C , Yong SL , Fang F , Li L , de la Fuente R , Wang L , Chen Q , Wang QK . Mutation in nuclear pore component NUP155 leads to atrial fibrillation and early sudden cardiac death. Cell 135: 1017‐1027, 2008.
 585. Zhou Z . T‐type calcium current in latent pacemaker cells isolated from cat right atrium. J Mol Cell Cardiol 26: 1211‐1219, 1994.
 586. Zhu XR , Wulf A , Schwarz M , Isbrandt D , Pongs O . Characterization of human Kv4.2 mediating a rapidly‐inactivating transient voltage‐sensitive K+ current. Receptors Channels 6: 387‐400, 1999.
 587. Zicha S , Fernández‐Velasco M , Lonardo G , L'Heureux N , Nattel S . Sinus node dysfunction and hyperpolarization‐activated (HCN) channel subunit remodeling in a canine heart failure model. Cardiovasc Res 66: 472‐481, 2005.
 588. Zicha S , Maltsev VA , Nattel S , Sabbah HN , Undrovinas AI . Post‐transcriptional alterations in the expression of cardiac Na+ channel subunits in chronic heart failure. J Mol Cell Cardiol 37: 91‐100, 2004.
 589. Zicha S , Xiao L , Stafford S , Cha TJ , Han W , Varro A , Nattel S . Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts. J Physiol 561: 735‐748, 2004.
 590. Zimmer T , Bollensdorff C , Haufe V , Birch‐Hirschfeld E , Benndorf K . Mouse heart Na+ channels: Primary structure and function of two isoforms and alternatively spliced variants. Am J Physiol Heart Circ Physiol 282: H1007‐H1017, 2002.
 591. Zingman LV , Hodgson DM , Bast PH , Kane GC , Perez‐Terzic C , Gumina RJ , Pucar D , Bienengraeber M , Dzeja PP , Miki T , Seino S , Alekseev AE , Terzic A . Kir6.2 is required for adaptation to stress. Proc Natl Acad Sci U S A 99: 13278‐13283, 2002.
 592. Zygmunt AC , Eddlestone GT , Thomas GP , Nesterenko VV , Antzelevitch C . Larger late sodium conductance in M cells contributes to electrical heterogeneity in canine ventricle. Am J Physiol Heart Circ Physiol 281: H689‐H697, 2001.
 593. Zygmunt AC , Goodrow RJ , Antzelevitch C . I(NaCa) contributes to electrical heterogeneity within the canine ventricle. Am J Physiol Heart Circ Physiol 278: H1671‐H1678, 2000.

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Article Title: Ion Channels in the Heart
 

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Daniel C. Bartos, Eleonora Grandi, Crystal M. Ripplinger. Ion Channels in the Heart . Compr Physiol 2015, 5: 1423-1464. doi: 10.1002/cphy.c140069