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.
Yuan
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C
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712.
Acosta
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D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D011189:Potassium Chloride; D012964:Sodium; D003042:Cocaine; D002118:Calcium