Calcium antagonists : mechanism of action on cardiac muscle and vascular smooth muscle : from the proceedings of the Meeting of the American Section of the International Society for Heart Research (ISHR), Hilton Head, South Carolina, September 21-24, 1983

INTRODUCTION: Role of ca++ in Contraction, and Wide Variety of Effects of Calcium Antagonists Nick SpereJakis The calcium antagonistic drugs are a relatively new class of drugs that have in common the effect of reducing Ca++ ion entry into excitable nerve and muscle cells through the voltage-dependent and time-dependent slow channels. Hence, these drugs are also known as Ca ++ entry blockers, slow channel blockers, or organic calcium antagonistis (to contrast with the inorganic calcium antagonists, such as Mn++, Co++, Mg++, and La+++). The organic structure of the calcium antagonistic drugs varies widely, and the chemical formulae of some of the major sub-classes of these drugs are depicted in Figure 1. VERAPAIlIL 0(100) .EPRIOIL .PlOIPIIiI IIlaUOIPINI g aCH3 ",Ca DDC, I ~CODC2H5 H,C , CH 3 H Pig. 1: The chemical structures of some calcium antagonists. The process of excitation-contraction coupling in cardiac muscle cells and in vascular smooth muscle cells is depicted in Figures 2 and 3, respectively. In myocardial cells, the Ca++ influx from the interstitial fluid into the intracellular fluid controls the force of contraction of the cells (and hence of the entire heart). Front Matter ....Pages i-xiii INTRODUCTION: Role of Ca++ in Contraction, and Wide Variety of Effects of Calcium Antagonists (Nick Sperelakis)....Pages 1-9 Calcium Channel Antagonists: Pharmacologic and Radioligand Binding Approaches to Mechanisms of Action (D. J. Triggle, R. A. Janis)....Pages 11-20 Effects of Calcium Slow Channel Blockers on the Slow Action Potentials of Cardiac Muscle and Vascular Smooth Muscle (Nick Sperelakis)....Pages 21-45 Voltage Clamp Studies Of Calcium Channel Blockage in the Heart (R. S. Kass, M. C. Sanguinetti)....Pages 47-62 Mechanisms of Selective CA Antagonist-Induced Vasodilation (C. Van Breemen, C. Cauvin, O. Hwang, P. Leyten, S. Lukeman, K. Meisheri et al.)....Pages 63-76 Action of Calcium Slow Channel Inhibitors on Cardiac and Vascular Smooth Muscle Membranes (Mohammed A. Matlib, Arnold Schwartz, A. DePover, G. Grupp, I. Grupp, S. W. Lee et al.)....Pages 77-93 Effects of Calcium Antagonists on Injured Cells (Philip D. Henry)....Pages 94-100 Antianginal Effects of Calcium Antagonists (John S. Schroeder)....Pages 101-110 Clinical Electrophysiology of the Calcium Antagonists (E. Rowland, D. M. Krikler)....Pages 111-117 Basic Features of The Frequency- and Voltage-Dependent Block By D600 of Calcium Channels in Ventricular Muscle (Terence F. McDonald, Dieter Pelzer, Wolfgang Trautwein)....Pages 118-136 Evidence for a Modulated Receptor Mechanism of Calcium Channel Blockade (C. W. Clarkson, M. Inazawa, S. Kanaya, L. M. Hondeghem, B. G. Katzung)....Pages 137-151 Effects of Calcium Antagonistic Drugs on Various Heart Tissues, Including Blockade of the Slow Channels and Depression of Postdrive Hyperpolarization. (P. A. Molyvdas, N. Sperelakis)....Pages 153-178 Effect of Nifedipine on Rat Papillary Muscle and Perfused Heart (P. Braveny, J. S. Juggi, G. Telahoun)....Pages 179-185 Excitation-Contraction Coupling in Rat Myocardium: Modulation with Verapamil and Calcium (Joseph M. Capasso)....Pages 187-202 The Potentially Direct Role of Intracellular Calcium Overload in the Electrophysiology of Cardiac Ischemia (William T. Clusin, Maurice Buchbinder, R. Hardwin Mead)....Pages 203-217 Mechanisms of the Beneficial Effects of Some Ca2+ Antagonists on the Ca2+-Paradox in Myocardium (N. S. Dhalla, P. K. Singal, S. Takeo, D. B. McNamara)....Pages 219-227 Comparative Effects of Ca Slow Channel Blockers on the Hamster Hereditary Cardiomyopathy (G. Jasmin, L. Proschek)....Pages 229-239 Calcium Antagonistic Agents: Uptake into Various Muscles and their Effects on Calcium Binding (David C. Pang, Nick Sperelakis)....Pages 241-256 The Effect of Verapamil on Lanthanum (La3+) Binding in the Isolated Rabbit Heart (S. A. Barman, J. T. Saari, M. D. Olson)....Pages 257-273 In Situ Small Blood Vessel Electrical Response to Verapamil in Spontaneously Hypertensive Rats (W. J. Stekiel, M. J. Burke, S. J. Contney, J. H. Lombard)....Pages 275-285 Comparison of Calcium Blocking Activities of Adenosine Potentiating Compounds With Calcium Blocking Drugs in Isolated Smooth Muscle and Atria (Y. Nakagawa, M. Gudenzi, S. Jamal Mustafa)....Pages 287-301 Effects of Inhibitors of Arachidonic Acid Metabolism and Calcium Entry on Hypoxic Contractions of the Isolated Canine Coronary Artery (Thomas J. Rimele, Paul M. Vanhoutte)....Pages 303-316 Effect of Diltia Zem on Calcium Cup Rents and Excitation-Contraction Coupling in Frog Twitch Muscle (H. Gonzalez-Serratos, R. Valle-Agilera, C. Phillips)....Pages 317-325 Inhibition of Human Platelet Aggregation and Calcium-Dependent, Phospholipase A2 Activity by Calcium Antagonists: Evidence for Intracellular Effects of Calcium Slow Channel Blockers (Richard C. Franson, Herbert Evans, Jayanti Thakkar, Nick Sperelakis)....Pages 327-338 Characterization of Cardiac Sarcoplasmic Reticulum: Dysfunction during primary myocardial ischemia: A potential source for intracellular calcium overload (Michael L. Hess, Stephen M. Krause)....Pages 339-352 From the Proceedings of the Meeting of the American Section of the International Society for Heart Research (ISHR) at Hilton Head, South Carolina, September 21-24, 1983