Yuan C, Acosta D
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712.
J Mol Cell Cardiol. 1994 Nov;26(11):1415-9. doi: 10.1006/jmcc.1994.1160.
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.
可卡因可产生正性和负性肌力作用。可卡因诱导负性肌力作用的机制尚不清楚。为了评估可卡因对心肌收缩力的抑制作用，研究了其对氯化钾诱导的去极化、肌浆网钙释放和肌膜钠钙交换的作用。在相对较高浓度（10⁻³ M）时，可卡因显著阻断氯化钾诱导去极化过程中胞质钙的升高，并显著抑制咖啡因引起的肌浆网钙释放。相反，低得多的可卡因浓度（10⁻⁷ M）显著降低肌膜钠钙交换。我们的结果表明，可卡因的负性肌力作用可能与浓度依赖性效应有关：较高浓度可能抑制肌浆网钙释放并阻断钙跨肌膜内流。相反，较低浓度会因肌膜钠钙交换体受损而导致正性肌力作用。
