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 microM for cocaine, but 90.0 microM 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.
Bai
H
H
Department of Legal Medicine, Osaka University Medical School, Japan.
Otsu
K
K
Islam
M N
MN
Kuroki
H
H
Terada
M
M
Tada
M
M
Wakasugi
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D002316:Cardiotonic Agents; C066444:cocaethylene; D003042:Cocaine; D002118:Calcium