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

D. C. Renard, F. J. Delaville, A. P. Thomas

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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 ~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 μM 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 β-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 μM 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.

Original languageEnglish (US)
Pages (from-to)H555-H567
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume266
Issue number2 35-2
Publication statusPublished - Apr 8 1994
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • caffeine
  • calcium current
  • contractility
  • sodium current

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