VERAPAMIL BLOCKADE OF SLOW Na⁺ AND Ca⁺⁺ RESPONSES IN MYOCARDIAL CELLS

¹ Department of Physiology, University of Virginia School of Medicine, Charlottesville, Virginia

Verapamil was used to characterize further the slow cation responses found in myocardial cells either normally or induced by pharmacological agents. Studies were made on chick embryonic hearts of various ages and on guinea-pig hearts. 1) The action potentials of 3-day-old chick embryonic hearts were unaffected by tetrodotoxin or only slightly affected in low Ca⁺⁺ (0.05 mM), demonstrating that young hearts do not possess fast Na⁺ channels and that a slow Na⁺ current must be the main inward current. Verapamil (2 µg/ml) rapidly blocked all excitability and contractions. 2) In 5-to 6-day hearts, tetrodotoxin depressed the maximal rate of rise of the action potential (+V_max) to about 10 V/sec, and verapamil, but not 1 mM Mn⁺⁺, blocked the electrical responses persisting in tetrodotoxin. Since Mn⁺⁺ should block any Ca⁺⁺ influx, verapamil must block slow Na⁺ responses. 3) In 15-day hearts, verapamil partially depressed the action potential plateau (without affecting + V_max) concomitant with electromechanical uncoupling. Verapamil also slowly produced a small depolarization, particularly in young hearts. 4) In isolated guinea-pig hearts perfused with normal solution, verapamil (2 µg/ml) depressed the contractions to about 10% at 3 minutes without greatly affecting the action potential plateau. Slow electrical responses with accompanying contractions, induced during perfusion with 27 mM K⁺ solution containing isoproterenol, caffeine or dibutyryl cyclic adenosine monophosphate, were abolished by verapamil (0.05 µg/ml) within 1 minute. +V_max and overshoot of the slow responses increased when [Ca⁺⁺]₀ was elevated and decreased when [Na⁺]₀ was lowered, indicating that both Ca⁺⁺ and Na⁺ are involved in the slow response. In conclusion, verapamil is not a specific blocker of Ca⁺⁺ responses, but it also blocks slow Na⁺ responses.

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