Direct cardiotoxic effects of cocaine and cocaethylene on isolated cardiomyocytes

We investigated the cardiotoxic effects of cocaine and cocaethylene on the Ca2+ flux responsible for excitation-contraction coupling in isolated ventricular rat myocytes. We simultaneously measured intracellular Ca2+ transients and cell length in isolated cardiac myocytes loaded with a fluorescent Ca2+ indicator, indo-1, during electrical field stimulation at 1 Hz. The cell length was estimated by video dimension analysis. We also measured the activities of Ca2+ ATPase and Ca2+ release channels of cardiac sarcoplasmic reticulum membrane vesicles. Both cocaine and cocaethylene produced significant decreases in both peak intracellular Ca2+ and the cell-contraction rate in a dose-dependent manner. The K0.5 for the reduction of peak intracellular Ca2+ was 157.5 μM for cocaine, but 90.0 μM for cocaethylene. Both cocaethylene and cocaine inhibited neither Ca2+ ATPase nor Ca2+ release channel activity. These results demonstrate that cocaethylene has a more potent direct negative inotropic action on cardiomyocytes, without preventing Ca2+ flux through the cardiac sarcoplasmic reticulum membrane.