Inhibitory effects of cocaine on Ca2+ transients and contraction in single cardiomyocytes
Renard, D.C.; Delaville, F.J.; Thomas, A.P.
American Journal of Physiology 266(2 Pt 2): H555-H567
1994
ISSN/ISBN: 0002-9513 PMID: 8141357 Document Number: 431165
The effects of cocaine on the Ca-2+ transient responsible for excitation-contraction coupling were studied in single rat heart cells loaded with the fluorescent Ca-2+ 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 Ca-2+ concentration ((Ca-2+)-i) and contraction simultaneously from the images of fluorescence. Cardiomyocytes maintained a basal (Ca-2+), of apprx 140 nM in presence or absence of cocaine. After electrical field stimulation, (Ca-2+)-i increased to a peak of 498 +- 25 nM under control conditions. This was reduced to a peak (Ca-2+), of 389 +- 25 nM after treatment with 50 mu-M cocaine. Cocaine also reduced the rate of rise of (Ca-2+)-i but did not affect the time to peak or the half time for resequestration of the released Ca-2+. The rate and extent of cell shortening was reduced by cocaine in parallel with the inhibition of the (Ca-2+), transient. Cocaine had no effect on the half time for relaxation. Cocaine did not modify the relationship between contraction and the elevation of (Ca-2+)-i over a range of extracellular Ca-2+ concentrations. The intracellular pool of Ca-2+ releasable by caffeine was also unaffected by cocaine. In the presence of the beta-adrenergic agonist isoproterenol, which caused a large enhancement of Peak (Ca-2+)-i and contraction, cocaine still inhibited both parameters. However, cocaine did not reverse the ability of isoproterenol to enhance the rate of Ca-2+ reuptake and cell relaxation. Whole cell voltage-clamp studies showed that 50 mu-M cocaine reduced both the Na+ current (50%) and the Ca-2+ 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 (Ca-2+)-i transients by cocaine.