AJP - Heart and Circulatory Physiology, Vol 266, Issue 2 555-H567, Copyright © 1994 by American Physiological Society

ARTICLES

Inhibitory effects of cocaine on Ca2+ transients and contraction in single cardiomyocytes

D. C. Renard, F. J. Delaville and A. P. Thomas
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

The effects of cocaine on the Ca2+ transient responsible for excitation-contraction coupling were studied in single rat heart cells loaded with the fluorescent Ca2+ indicator fura 2. A high-speed imaging technique using a charge-coupled device as detector and transient image store [O'Rourke et al., Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H230-H242, 1990] was used to measure cytosolic free Ca2+ concentration ([Ca2+]i) and contraction simultaneously from the images of fluorescence. Cardiomyocytes maintained a basal [Ca2+]i of approximately 140 nM in presence or absence of cocaine. After electrical field stimulation, [Ca2+]i increased to a peak of 498 +/- 25 nM under control conditions. This was reduced to a peak [Ca2+]i of 389 +/- 25 nM after treatment with 50 microM cocaine. Cocaine also reduced the rate of rise of [Ca2+]i but did not affect the time to peak or the half time for resequestration of the released Ca2+. The rate and extent of cell shortening was reduced by cocaine in parallel with the inhibition of the [Ca2+]i transient. Cocaine had no effect on the half time for relaxation. Cocaine did not modify the relationship between contraction and the elevation of [Ca2+]i over a range of extracellular Ca2+ concentrations. The intracellular pool of Ca2+ releasable by caffeine was also unaffected by cocaine. In the presence of the beta-adrenergic agonist isoproterenol, which caused a large enhancement of peak [Ca2+]i and contraction, cocaine still inhibited both parameters. However, cocaine did not reverse the ability of isoproterenol to enhance the rate of Ca2+ reuptake and cell relaxation. Whole cell voltage-clamp studies showed that 50 microM cocaine reduced both the Na+ current (50%) and the Ca2+ current (30%). These data suggest that sarcolemmal ion channels are the primary site that, in cardiac muscle, mediate the negative inotropic effects and the suppression of [Ca2+]i transients by cocaine.

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