Effects of Calcium Antagonistic Drugs on Various Heart Tissues, Including Blockade of the Slow Channels and Depression of Postdrive Hyperpolarization.

Abstract

The force of contraction of the heart muscle is regulated by the Ca⁺⁺ ions that enter the myocardial cell during excitation (Fabiato & Fabiato, 1979). The Ca⁺⁺ influx occurs through the voltage-dependent and time-dependent slow channels of the cell membrane, and can be inhibited by specific blockers. These inhibitors can be inorganic ions,like Mn⁺⁺ and La⁺⁺⁺, or organic compounds like verapamil, nifedipine, diltiazem, and bepridil (Kohlhardt et al., 1972; Shigenobu et al., 1974; Kohlhardt and Fleckenstein, 1977; Vogel et al., 1979; Sperelakis, 1981). These drugs are called calcium antagonists or “calcium entry blockers” because of their ability to block the slow inward current in myocardial cells and in vascular smooth muscle. Since some of these drugs, like verapamil, methoxy-verapamil (D600), and nifedipine also block the slow Na⁺ channels of young embryonic chick hearts, these drugs are more accurately described as “slow channel blockers” (Shigenobu et al., 1974; Lee & Tsien, 1983; Kojima & Sperelakis, 1983).