Inhibitory effect of cocaine on calcium mobilization in cultured rat myocardial cells.

Cocaine can produce both positive and negative inotropy. The mechanism of cocaine-induced negative inotropy is poorly understood. In order to evaluate the inhibitory effect of cocaine on myocardial contractility, its action on potassium chloride-induced depolarization, release of calcium from sarcoplasmic reticulum, and sarcolemmal sodium-calcium exchange were studied. At a relatively high concentration (10(-3) M), cocaine significantly blocked an elevation of cytosolic calcium during potassium chloride-induced depolarization and significantly inhibited the release of calcium from sarcoplasmic reticulum by caffeine. In contrast, a much lower concentration of cocaine (10(-7) M) significantly reduced sarcolemmal sodium-calcium exchange. Our results suggest that the negative inotropic action of cocaine may be related to a concentration-dependent effect: higher concentrations may inhibit calcium release from sarcoplasmic reticulum and block calcium influx across the sarcolemma. In contrast, lower concentrations would lead to a positive inotropic effect because of an impaired sarcolemmal sodium-calcium exchanger.