title: Inhibitory effects of cocaine on Ca2+ transients and contraction in single cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: D C
authors.initials: DC
authors.lastname: Renard
authors.forename: F J
authors.initials: FJ
authors.lastname: Delaville
authors.forename: A P
authors.initials: AP
authors.lastname: Thomas
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology
chemical_list: D014701:Veratridine; D003042:Cocaine; D007545:Isoproterenol; D002118:Calcium