Effects of Calcium Slow Channel Blockers on the Slow Action Potentials of Cardiac Muscle and Vascular Smooth Muscle

  • Nick Sperelakis
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 39)


The work of the author and his colleagues reviewed and summaried in this article was supported in part by grants from the National Institutes of Health (HL-31942), Wallace Laboratories, Smith, Kline and French Laboratories, and Miles Institute for Medical Research.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brown, HF: Electrophysiology of the sinoatrial node. Physiological Reviews (62): 505–530, 1982.PubMedGoogle Scholar
  2. 2.
    Brown HF, DiFrancesco D: Voltage clamp investigations of membrane currents underlying pacemaker activity in rabbit sinoatrial node. J Physiol Lond (308): 331–335, 1980.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Carty D, Sperelakis N, Villar-Palasi C: Ca++-antagonistic drugs reverse cyclic AMP-dependent phosphorylation of heart sarcolemmal proteins, (unpublished observations).Google Scholar
  4. 4.
    Fabiato A, Fabiato F: Calcium and cardiac excitation-contraction coupling. Ann Rev Physiol (41): 473–484, 1979.CrossRefGoogle Scholar
  5. 5.
    Ferrier GR, Moe GK: Effect of calcium in acetyl strophanthidin-induced transient depolarizations in canine Purkinje tissue. Circ Res (33): 508–515, 1973.PubMedCrossRefGoogle Scholar
  6. 6.
    Fleckenstein A, Tritthart H, Doring HJ, Byon KY: Bay a 1040-ein hochactiver inhibitor der electro-mechanischen Koppelungspzozesse in warmbluter-Myokard Arzwein-Forsch (Drug Res) (22): 22–33, 1972.Google Scholar
  7. 7.
    Goto J, Sperelakis N: Depression of automaticity of the rabbit SA node by nifedipine and bepridil. Europ J Pharmacol (in press), 1984.Google Scholar
  8. 8.
    Grant AO, Strauss HC: Intracellular potassium activity in rabbit sinoatrial node. Circ Res (51): 271–279, 1982.PubMedCrossRefGoogle Scholar
  9. 9.
    Harder DR, Sperelakis N: Action potentials induced in guinea pig arterial smooth muscle by tetraethylammonium. Am J Physiol/Cell Physiol (237): C75–C80, 1979.Google Scholar
  10. 10.
    Harder DR, Sperelakis N: Bepridil blockade of Ca++-dependent action potentials in vascular smooth muscle of dog coronary artery. J Cardiovasc Pharmacol (3): 906–914, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Hescheler J, Pelzer D, Trube G, Trautwein W: Does the organic calcium channel blocker D600 act from inside or outside on the cardiac cell membrane? Pflugers Arch (393): 287–291, 1982.PubMedCrossRefGoogle Scholar
  12. 12.
    Hondeghem S, Kanaya P, Arlock, Katzung B: Verapamil and diltiazem block inactivated calcium channels. Circulation (66): 11293, 1982.Google Scholar
  13. 13.
    Josephson I, Sperelakis N: On the ionic mechanism underlying adrenergic- cholinergic antagonism in ventricular muscle. J Gen Physiol (79): 69–86, 1982.PubMedCrossRefGoogle Scholar
  14. 14.
    Kojima M, Sperelakis N: Calcium antagonistic drugs differ in ability to block the slow Na+ channels of young embryonic chick hearts. Eur J Pharmacol (94): 9–18, 1983.PubMedCrossRefGoogle Scholar
  15. 15.
    Kohlhardt M, Krause H, Kubler M, Herdey A: Kinetics of inactivation and recovery of the slow inward current in mammalian ventricular myocardium. Pflugers Arch (355): 1–17, 1975.PubMedCrossRefGoogle Scholar
  16. 16.
    Kohlhardt M, Fleckenstein A: Inhibition of slow inward current by nifedipine in mammalian ventricular myocardium. Naunyn Schmiedbergs Arch Pharmacol (298): 267–272, 1977.CrossRefGoogle Scholar
  17. 17.
    Labrid C, Grosset A, Dureng G, Mironneau J, Duchenne–Marullaz P: Some membrane interactions with bepridil, a new antianginal agent. J Pharmacol Exp Ther (211): 546–554, 1979.PubMedGoogle Scholar
  18. 18.
    Li T, Sperelakis N: Calcium antagonist blockade of slow action potentials in cultured chick heart cells. Can J Physiol Pharmacol (61): 957–966, 1983.PubMedCrossRefGoogle Scholar
  19. 19.
    McLean MJ, Shigenobu K, Sperelakis N: Two pharmacological types of slow Na+ channels as distinguished by verapamil blockade. Europ J Pharmacol (26): 379–382, 1974.CrossRefGoogle Scholar
  20. 20.
    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), 162–69, 1983a.PubMedCrossRefGoogle Scholar
  21. 21.
    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, 1983b.PubMedCrossRefGoogle Scholar
  22. 22.
    Mras S, Sperelakis N: Bepridil (CERM-1978) blockade of action potentials in cultured rat aortic smooth muscle cells. Europ J Pharmacol (71): 13–19, 1981.CrossRefGoogle Scholar
  23. 23.
    Mras S, Sperelakis N: Comparison of [3H] bepridil and [3H] verapamil uptake into rabbit aortic rings. J Cardiovasc Pharmacol (4): 777–783, 1982.PubMedCrossRefGoogle Scholar
  24. 24.
    Osterrieder W, Yang QF, Trautwein W: Effects of barium on the membrane currents of the rabbit SA node. Pflugers Arch (394): 78–84, 1982.PubMedCrossRefGoogle Scholar
  25. 25.
    Pang D, Sperelakis N: Inhibitory action of bepridil (CERM-1978) on calcium binding to cardiac sarcolemma of guinea pig. Biochem Pharmacol (30): 2356–2358, 1981.PubMedCrossRefGoogle Scholar
  26. 26.
    Pang DC, Sperelakis N: Veratridine stimulation of calcium uptake by embryonic heart cells in culture. J Molec Cell Cardiol (14): 703–710, 1982.CrossRefGoogle Scholar
  27. 27.
    Pang DC, Sperelakis N: Nifedipine, diltiazem, bepridil and verapamil uptakes into cardiac and smooth muscles. Europ J Pharmacol (87): 199–297, 1983a.CrossRefGoogle Scholar
  28. 28.
    Pang DC, Sperelakis N: Uptake of 3-nitrendipine into cardiac and smooth muscles. Biochem Pharmacol (32): 1660–1663, 1983b.PubMedCrossRefGoogle Scholar
  29. 29.
    Pelzer D, Trautwein W, McDonald TF: Calcium channel block and recovery from block in mammalian ventricular muscle treated with organic channel inhibitors. Pflugers Arch (394): 97–105, 1982.PubMedCrossRefGoogle Scholar
  30. 30.
    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
  31. 31.
    Saikawa T, Nagamoto Y, and Arita M: Electrophysiologic effects of diltiazem, a new slow channel inhibitor, on canine cardial fibers. Jap Heart J. (18): 235–245, 1977.PubMedCrossRefGoogle Scholar
  32. 32.
    Schneider JA, Sperelakis N: Slow Ca++ and Na+ responses induced by isoproterenol and methylxanthines in isolated perfused guinea pig hearts exposed to elevated K+. J Molec Cell Cardiol (7): 249–273, 1975.CrossRefGoogle Scholar
  33. 33.
    Shigenobu K, Schneider JA, Sperelakis N: Verapamil blockade of slow Na+ and Ca++ responses in myocardial cells. J Pharmacol Exp Therap (190): 280–288, 1974.Google Scholar
  34. 34.
    Sperelakis N: Origin of the cardiac resting potential. IN: Berne RM, Sperelakis N (eds) Handbook of Physiology, The Cardiovascular System, Vol. 1: The Heart. Am Physiol Soc, Bethesda, 1979, pp 187–267.Google Scholar
  35. 35.
    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. Martinus Nijhoff, The Hague, 1980, pp 221–262.CrossRefGoogle Scholar
  36. 36.
    Sperelakis N: Electrophysiology of vascular smooth muscle of coronary artery. In: Kalsner S (ed) The Coronary Artery. Croom Helm, Ltd, London, 1982, pp 118–167.Google Scholar
  37. 37.
    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. Raven Press, New York, 1983, (in press).Google Scholar
  38. 38.
    Sperelakis N, Mras S: Depression of contractions of rabbit aorta and guinea pig vena cava by mesudipine and other slow channel blockers. Blood Vessels (20): 172–183, 1983.PubMedGoogle Scholar
  39. 39.
    Sperelakis N, Schneider J A: A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell. Am J Cardiol (37): 1079–1085, 1976.PubMedCrossRefGoogle Scholar
  40. 40.
    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
  41. 41.
    Yanagihara K, Irisawa H: Potassium current during the pacemaker depolarization in rabbit sinoatrial node cell. Pflugers Arch (388): 255–260, 1980.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • Nick Sperelakis

There are no affiliations available

Personalised recommendations