Abstract
The Ca-dependent, slow inward current (Isi) is of major importance to the heart since the current is intimately connected with excitation-contraction coupling, sinoatrial rhythm, atrioventricular transmission, and certain patterns of dysrhythmia. A variety of organic agents, of which verapamil and D600 (methoxyverapamil) have been best studied, block Ca channels and thereby reduce Isi in cardiac tissue (1–4). The consequences of this action include a depression of the action potential plateau and contraction in ventricular muscle (3,5) as well as a reduction in the sinus rate and a prolongation of conduction time through the AV node (6).
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References
Kohlhardt M, Bauer B, Krause H, Fleckenstein A: Differentiation of the transmembrane Na and Ca channel in mammalian cardiac fibres by the use of specific inhibitors. Pflugers Arch. (335): 309–322, 1972.
Kass RS, Tsien RW: Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibres. J. gen. Physiol. (66): 169–192, 1975.
Nawrath H, Ten Eick RE, McDonald TF, Trautwein W: On the mechanism underlying the action of D600 on slow inward current and tension in mammalian myocardium. Circulation Res. (40): 408–414, 1977.
Noma A, Trautwein W: Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell. Pflugers Arch. (377): 193–200, 1978.
Bayer R, Hennekes R, Kaufmann R, Mannhold R: Inotropic and electrophysiological action of verapamil and D600 in mammalian myocardium. I. Pattern of iontropic effects of the racemic compounds. Naunyn-Schmiedeberg’s Arch. Pharmac. (290): 49–68, 1975.
Wit AL, Cranefield PF: Effect of verapamil on the sinoatrial and atrioventricular nodes of the rabbit and the mechanisms by which it arrests re-entrant atrioventricular nodal tachycardia. Circulation Res. (35): 413–425, 1974.
McCans JL, Lindenmayer GE, Munson RG, Evans RW, Schwartz A: A dissociation of positive staircase (Bowditch) from ouabain-induced positive inotropism; use of verapamil. Circulation Res. (35): 439–447, 1974.
Ehara T, Kaufmann R: The voltage- and time-dependent effects of (-)-verapamil on the slow inward current in isolated cat ventricular myocardium. J. Pharmac exp. Ther. (207): 49–55, 1978.
McDonald TF, Pelzer D, Trautwein W: On the mechanism of slow calcium channel block in heart. Pflugers Arch. (385): 175–179, 1980.
Pelzer D, Trautwein W, McDonald TF: Calcium channel block and recovery from block in mammalian ventricular muscle treated with organic channel inhibitors. Pflügers Arch. (394): 97–105, 1982.
Strichartz, GR: The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J. gen. Physiol. (62): 37–57, 1973.
Hille B: Local anestheticsrhydrophilic and hydrophobic pathways for the drug-receptor reaction. J. gen. Physiol. (69): 497–515, 1977.
McDonald TF, Pelzer D, Trautwein W: Cat ventricular muscle treated with D600: effects on calcium and potassium currents. J. Physiol, (in the Press), 1984.
McDonald TF, Pelzer D, Trautwein W: Cat ventricular muscle treated with D600: characteristics of calcium channel block and unblock. J. Physiol, (in the Press), 1984.
Lee KS, Tsien RW: Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature (Lond.) (302): 790–794, 1983.
McDonald TF, Trautwein W: Membrane currents in cat myocardium; separation of inward and outward components. J. Physiol. (274): 193–216, 1978.
Trautwein W, McDonald TF, & Tripathi, O: Calcium conductance and tension in mammalian ventricular muscles. Pflügers Arch. (354), 55–74, 1975.
McDonald TF, Pelzer D, Trautwein W: Does the calcium current modulate the contraction of the accompanying beat? A study of E-C coupling in mammalian ventricular muscle using cobalt ions. Circulation Res. 49: 576–583, 1981.
Kenyon JL, Gibbons WR: 4-Aminopyrimidine and the early outward current of sheep cardiac Purkinje fibres. J. gen. Physiol. 73, 139–157, 1979.
Carmeliet E, Vereecke J: Electrogenesis of the action potential and automaticity. In Handbook of Physiology, The Cardiovascular System, vol. I, The Heart, ed. Berne, RM, pp. 269–334. Maryland: American Physiological Society, 1979.
Siegelbaum SA, Tsien RW: Calcium-activated transient outward current in calf cardiac Purkinje fibres. J. Physiol (299): 485–506, 1980.
Boyett MR: A study of the effect of the rate of stimulation on the transient outward current in sheep cardiac Purkinje fibres. J. Physiol: (319), 1–22, 1981.
Reuter H, Scholz H: A study of the ion selectivity and the kinetic properties of the calcium dependent slow inward current in mammalian cardiac muscle. J. Physiol. (264): 17–47, 1977.
Narahashi T: Chemicals as tools in the study of excitable membranes. Physiol. Rev. (54): 813–889, 1974.
Bustamante JO, McDonald TF: Sodium currents in segments of human heart cells. Science (220): 320–321, 1983.
Khodorov B.I. Sodium inactivation and drug-induced immobilization of the gating charge in nerve membrane. Prog. Biophys. molec. Biol (37) 49–89, 1981.
Cahalan MD, Shapiro BI, Aimers W: Relationship between inactivation of sodium channels and block by quaternary derivatives of local anesthetics and other compounds. In Progress in Anesthiology, ed. Fink BR, vol 2., Molecular Mechanisms of Anesthesia, pp. 17–33. New York, Raven Press: 1980.
Dörrscheidt-Käfer M: The action of D600 on frog skeletal muscle; facilitation of excitation-contraction coupling. Pfliigers Arch. (369): 259–267, 1977.
Hescheler J, Pelzer D, Trube G, Trautwein W: Do organic calcium channel blockers act from inside or outside on the cardiac cell membrane? Pflügers Arch. (393): 287–291, 1982.
Antman EM, Stone PH, Muller JE, Braunwald E: Calcium channel blocking agents in the treatment of cardiovascular disorders. I. Basic and clinical electrophysiologic effects. Ann. int. Med. (93): 875–885, (1980).
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© 1984 Martinus Nijhoff Publishing, Boston
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McDonald, T.F., Pelzer, D., Trautwein, W. (1984). Basic Features of The Frequency- and Voltage-Dependent Block By D600 of Calcium Channels in Ventricular Muscle. In: Sperelakis, N., Caulfield, J.B. (eds) Calcium Antagonists. Developments in Cardiovascular Medicine, vol 39. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3810-9_10
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DOI: https://doi.org/10.1007/978-1-4613-3810-9_10
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