The Slow Action Potential and Properties of the Myocardial Slow Channels

  • Nicholas Sperelakis
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 34)


Hormones and neurotransmitters play an important role in regulating the force of contraction of the heart. The force of contraction of the heart is controlled by the Ca2+ influx across the cell membrane during the action potential (AP) in the process of excitation-contraction coupling (fig. 8-1). This Ca2+ influx occurs through the voltage-dependent and time-dependent gated slow channels of the cell membrane. This chapter briefly reviews and summarizes some of the important properties of the myocardial slow channels, particularly their dependence on metabolism and their regulation by cyclic AMP. In addition, the slow action potentials and their possible role in cardiac arrhythmias will be briefly discussed.


Cholera Toxin Myocardial Cell Slow Channel Positive Inotropic Agent Embryonic Chick Heart 
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  1. 1.
    Schneider JA, Sperelakis N: The demonstration of energy dependence of the isoproterenol-induced transcellular Ca+ + current in isolated perfused guinea pig hearts: an explanation for mechanical failure in ischemic myocardium. J Surg Res 16: 389–403, 1974.PubMedCrossRefGoogle Scholar
  2. 2.
    Sperelakis N: Electrophysiology of vascular smooth muscle of coronary artery. In: Kalsner S (ed) The coronary artery. Croom Helm, 1982, pp 118–167.Google Scholar
  3. 3.
    Pappano AJ: Calcium-dependent action potentials produced by catecholamines in guinea pig atrial mucle fibers depolarized by potassium. Circ Res 27: 379–390, 1970.PubMedCrossRefGoogle Scholar
  4. 4.
    Sperelakis N: Changes in membrane electrical properties during development of the heart. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. The Hague: Martinus Nijhoff, 1980, pp 221–262.CrossRefGoogle Scholar
  5. 5.
    Lee KS, Tsien RW: Reversal of current through calcium channels in dialysed single heart cells. Nature 297: 498–501, 1982.PubMedCrossRefGoogle Scholar
  6. 6.
    Fabiato A, Fabiato F: Calcium and cardiac excitation-contraction coupling. Annu Rev Physiol 41: 473–484, 1979.PubMedCrossRefGoogle Scholar
  7. 7.
    Josephson I, Renaud JF, Vogel S, McLean M, Sperelakis N: Mechanism of the histamine-induced positive inotropic action in cardiac muscle. Eur J Pharmacol 35: 393–398, 1976.PubMedCrossRefGoogle Scholar
  8. 8.
    Shigenobu K, Sperelakis N: Ca+ + current channels induced by catecholamines in chick embryonic hearts whose fast Na+ channels are blocked by tetrodotoxin or elevated K. Circ Res 31: 932–952, 1972.PubMedCrossRefGoogle Scholar
  9. 9.
    Freer RJ, Pappano AJ, Peach MJ, Bing KT, McLean MJ, Vogel SM, Sperelakis N Mechanism of the positive inotropic effect of angiotensin II on isolated cardiac muscle. Circ Res 39: 178–183, 1976.Google Scholar
  10. 10.
    Reuter H, Stevens CF, Tsien RW, Yellen G: Properties of single calcium channels in cardiac cell culture. Nature 297: 501–504, 1982.PubMedCrossRefGoogle Scholar
  11. 11.
    Schneider JA, Sperelakis N: Valinomycin blockade of slow channels in guinea pig hearts perfused with elevated K+ and isoproterenol. Eur J Pharmacol 27: 349–354, 1974.PubMedCrossRefGoogle Scholar
  12. 12.
    Shigenobu K, Schneider JA, Sperelakis N: Verapamil blockade of slow Na+ and Ca2+ responses in myocardial cells. J Pharmcol Exp Ther 190: 280–288, 1974.Google Scholar
  13. 13.
    Reuter H, Scholz H: The regulation of the calcium conductance of cardiac muscle by adrenaline. J Physiol (Load) 264: 49–62, 1977.Google Scholar
  14. 14.
    Sperelakis N, Schneider JA: A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell. Am J Cardiol 37: 1079–1085, 1976.PubMedCrossRefGoogle Scholar
  15. 15.
    Watanabe AM, Besch HR Jr: Cyclic adenosine monophosphate modulation of slow calcium influx channels in guinea pig hearts. Circ Res 35: 316–324, 1974.CrossRefGoogle Scholar
  16. 16.
    Tsien RW, Giles W, Greengard P: Cyclic AMP mediates the effects of adrenaline on cardiac Purkinje fibers. Nature [New Biol) 240: 181–183, 1972.Google Scholar
  17. 17.
    Josephson I, Sperelakis N: 5’-Guanylimidodiphosphate stimulation of slow Ca++ current in myocardial cells. J Mol Cell Cardiol 10: 1157–1166, 1978.PubMedCrossRefGoogle Scholar
  18. 18.
    Metzer H, Lindner E: The positive inotropic-acting forskolin, a potent adenylate cyclase activator. Arzneim Forsch 31: 1248–1250, 1981.Google Scholar
  19. 19.
    Vogel S, Sperelakis N: Induction of slow action potentials by microiontophoresis of cyclic AMP into heart cells. J Mol Cell Cardiol 13: 51–64, 1981.PubMedCrossRefGoogle Scholar
  20. 20.
    Li T, Sperelakis N: Stimulation of slow action potentials in guinea-pig papillary muscle cells by intracellular injection of cAMP, Gpp(NH)p, and cholera toxin. Circ Res 52: 111–117, 1983.PubMedCrossRefGoogle Scholar
  21. 21.
    Vogel S, Sperelakis N: Valinomycin blockade of myocardial slow channels is reversed by high glucose. Am J Physiol 235: H46 - H51, 1978.PubMedGoogle Scholar
  22. 22.
    Wahler GM, Sperelakis N: Similar metabolic dependence of stimulated and unstimulated myocardial slow channels. Can J Physiol Pharmacol, 1983 (submitted for publication).Google Scholar
  23. 23.
    Rinaldi ML, Capony J-P, Demaille JG: The cyclic AMP-dependent modulation of cardiac sarcolemmal slow calcium channels. J Mol Cell Cardiol 14: 279–289, 1982.PubMedCrossRefGoogle Scholar
  24. 24.
    Vogel S, Sperelakis N, Josephson I, Brooker G: Fluoride stimulation of slow Ca++ current in cardiac muscle. J Mol Cell Cardiol 9: 461–475, 1977.PubMedCrossRefGoogle Scholar
  25. 25.
    Hescheler J, Pelzer D, Trube G, Trautwein W: Does the organic calcium channel blocker D-600 act from inside or outside on the cardiac cell membrane? Pflugers Arch 393: 287–291, 1982.PubMedCrossRefGoogle Scholar
  26. 26.
    Isenberg G: Cardiac Purkinje fibers: Ca2+ controls the potassium permeability via the conductance components gk1 and gk2. Pflugers Arch 371: 77–85, 1977.PubMedCrossRefGoogle Scholar
  27. 27.
    Bkaily G, Sperelakis N: Injection of protein kinase inhibitor into cultured heart cells blocks the calcium slow channels. Science, 1983 (submitted for publication).Google Scholar
  28. 28.
    Chesnais JM, Coraboeuf E, Sauvain MP, Vassas JM: Sensitivity to H, Li and Mg ions of the slow inward sodium current in frog atrial fibres. J Mol Cell Cardiol 7: 627–642, 1975.PubMedCrossRefGoogle Scholar
  29. 29.
    Vogel S, Sperelakis N: Blockade of myocardial slow inward current at low pH. Am J Physiol. 233: C99 - C103, 1977.PubMedGoogle Scholar
  30. 30.
    Belardinelli L, Vogel SM, Sperelakis N, Rubio R, Berne RM: Restoration of inward slow current in hypoxic heart muscle by alkaline pH. J Mol Cell Cardiol 11: 877–892, 1979.PubMedCrossRefGoogle Scholar
  31. 31.
    Josephson I, Sperelakis N: On the ionic mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle. J Gen Physiol 79: 69–86, 1982.PubMedCrossRefGoogle Scholar
  32. 32.
    Molyvdas P-A, Sperelakis N: Comparison of the effects of several calcium antagonistic drugs (slow-channel blockers) on the electrical and mechanical activities of guinea pig papillary muscle. J Cardiovasc Pharmacol 5: 162–169, 1983.PubMedCrossRefGoogle Scholar
  33. 33.
    Molyvdas P-A, Sperelakis N: Comparison of the effects of several calcium antagonistic drugs on the electrical activity of guinea pig Purkinje fibers. Eur J Pharmacol 88: 205–214, 1983.PubMedCrossRefGoogle Scholar
  34. 34.
    Li T, Sperelakis N: Calcium antagonist blockade of slow action potentials in cultured chick heart cells. Can J Physiol Pharmacol, 1983 (in press).Google Scholar
  35. 35.
    Kojima M, Sperelakis N: Calcium antagonistic drugs differ in blockade of slow Na+ channels in young embryonic chick hearts. Eur J Pharmacol, 1983 (submitted for publication).Google Scholar
  36. 36.
    Vogel S, Crampton R, Sperelakis N: Blockade of myocardial slow channels by Bepridil (CERM-1978). J Pharmacol Exp Ther 210: 378–385, 1979.PubMedGoogle Scholar
  37. 37.
    Pang DC, Sperelakis N: Nifedipine, diltiazem, verapamil and bepridil uptakes into cardiac and smooth muscles. Eur J Pharmacol 87: 199–207, 1983.PubMedCrossRefGoogle Scholar
  38. 38.
    Pang DC, Sperelakis N: Uptakes of calcium antagonists into mucles as related to their lipid solubilities. Biochem Pharmacol, 1983 (in press).Google Scholar
  39. 39.
    Pang DC, Sperelakis N: Differential actions of calcium antagonists on calcium binding to cardiac sarcolemma. Eur J Pharmacol 81: 403–409, 1982.PubMedCrossRefGoogle Scholar
  40. 40.
    Josephson I„ Sperelakis N: Local anesthetic blockade of Caz+-mediated action potentials in cardiac muscle. Eur J Pharmacol 40: 201–208, 1976.PubMedCrossRefGoogle Scholar
  41. 41.
    Lynch C, Vogel S, Sperelakis N: Halothane depression of myocardial slow action potentials. Anesthesiology 55: 360–368, 1976.Google Scholar
  42. 42.
    Sperelakis N, Belardinelli L, Vogel SM: Electrophysiological aspects during myocardial ischemia. In: Hayase S, Murao S (eds) Proceedings of 8th world congress of cardiology. Amsterdam: Excerpta Medica, 1979, pp 229–236.Google Scholar
  43. 43.
    Cukierman S, Paes de Carvalho A: Slow response excitation: dependence on rate and rhythm. In: Paes de Carvalho A, Hoffman BF, Lieberman M (eds) Normal and abnormal conduction in the heart. Mt Kisco NY: Futura, 1982, pp 413–428.Google Scholar
  44. 44.
    Masuda MO, Paula-Carvalho M, Paes de Carvalho A: Excitability and propagation of slow responses in rabbit atrium partially depolarized by added K+ and Baz+. In: Paes de Carvalho A, Hoffman BJ, Lieberman M (eds) Normal and abnormal conduction in the heart. Mt Kisco NY: Futura, 1982, pp 397–412.Google Scholar
  45. 45.
    Sperelakis, N, Mayer G, Macdonald R: Velocity of propagation in vertebrate cardiac muscles as functions of tonicity and [K+]0. Am J Physiol 219: 952–963, 1970.PubMedGoogle Scholar
  46. 46.
    Dodge FA, Cranefield PF: Nonuniform conduction in cardiac Purkinje fibers. In: Paes de Carvelho A, Hoffman BF, Lieberman M (eds) Normal and abnormal conduction in the heart. Mt Kisco NY: Futura Publishing Company, p 379–396.Google Scholar
  47. 47.
    Cranefield PF: The conduction of the cardiac impulse. Mt Kisco NY, 1975.Google Scholar
  48. 48.
    Cranefield PF, Dodge FA: Slow conduction in the heart. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. The Hague: Martinus Nijhoff, 1980, pp 149–171.CrossRefGoogle Scholar
  49. 49.
    Marban E, Tsien RW: Enhancement of calcium current during digitalis inotropy in mammalian heart: positive feed-back regulation by intracellular calcium? J Physiol 329: 589–614, 1982.PubMedGoogle Scholar
  50. 50.
    Lazzara R, Scherlag B: Role of the slow current in the generation of arrhythmias in ischemic myocardium. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. The Hague: Martinus Nijhoff, 1980, pp 399–416.CrossRefGoogle Scholar
  51. 51.
    Zipes DP, Rinkenberger RL, Heger JJ, Prystowsky EN: The role of the slow inward current in the genesis and maintenance of supraventricular tachyarrhythmias in man. In: Zipes DP, Bailey JC, Elharrar V (eds) The slow inward current and cardiac arrhythmias. The Hague: Martinus Nijhoff, 1980, 481–506.CrossRefGoogle Scholar
  52. 52.
    Lehmkuhl D, Sperelakis N: Electrical activity of cultured heart cells. In: Tanz RD, Kavaler F, Roberts J (eds) Factors influencing myocardial contractility. New York: Academic, 1967, pp 245–278.Google Scholar
  53. 53.
    Ferrier GR, Moe GK: Effect of calcium on acetyl 57. strophanthidin-induced transient depolarizations in canine Purkinje tissue. Circ Res 33: 508–515, 1973.PubMedCrossRefGoogle Scholar
  54. 54.
    Kass RS, Tsien RS, Weingart R: Ionic basis of transient inward current induced by strophanthidin in 58. cardiac Purkinje fibres. J Physiol (Lond) 281: 209–226, 1978.Google Scholar
  55. 55.
    Schneider JA, Sperelakis N: Slow Ca2+ and Na responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K. J Mol Cell Cardiol 7: 249–273, 1975.PubMedCrossRefGoogle Scholar
  56. 56.
    Sperelakis N: Properties of calcium-dependent slow action potentials, and their possible role in arrhythmias. In: Opie LH, Krebs R (eds) Calcium antagonists and cardiovascular disease. New York: Raven, 1983.Google Scholar
  57. 57.
    Sperelakis N: Cyclic AMP and phosphorylation in regulation of Ca2+ influx into myocardial cells, and blockade by calcium antagonistic drugs. Am Heart J, 1983.Google Scholar
  58. 58.
    Sperelakis N: Origin of the cardiac resting potential. In: Berne RM, Sperelakis N (eds) Handbook of physiology, the cardiovascular system, vol 1: the heart. Bethesda MD: American Physiological Society, 1979, pp 187–267.Google Scholar

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© Springer Science+Business Media Dordrecht 1984

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  • Nicholas Sperelakis

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