Activation of the voltage-dependent Ca2+ channel in rat heart cells by dihydropyridine derivatives

The two dihydropyridines Bay K8644 and CGP 28392 increase 45Ca2+ influx in cultured rat cardiac cells with half-maximal effects at 2 nM and 30 nM respectively at a membrane potential of -75 mV. This stimulation of Ca2+ uptake is inhibited by nitrendipine, verapamil and bepridil. Ca2+ channel activation produced by Bay K8644 and CGP 28392 has been compared with Ca2+ channel activation produced by depolarization. There is no addition between the effects of drugs activating the Ca2+ channel and the effects of depolarization suggesting that Bay K8644 and CGP 28392 work preferentially on polarized membranes. 45Ca2+ flux experiments yielded results which are in excellent agreement with electrophysiological and contraction data obtained with the same cells in culture. Dose-response curves for the physiological effects of the drugs are observed over the same range of concentrations as their inhibition of [3H]nitrendipine binding to its receptor.