Inhibition by cocaine of excitation-contraction coupling in isolated cardiomyocytes

G. Stewart, E. Rubin, A. P. Thomas

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The effects of cocaine on the Ca2+ fluxes responsible for excitation-contraction coupling were studied in isolated ventricular rat heart cells loaded with the fluorescent Ca2+ indicator fura-2. Ca2+ transients in response to electrical field stimulation were followed using a fluorescence ratio method in which excitation light was alternated with 5-ms resolution. The cardiomyocytes maintained a basal cytosolic Ca2+ concentration of ~70 nM, which increased to a peak of 450 nM in response to each electrical stimulus. The addition of cocaine (10 μM) to cells stimulated at 0.4 Hz decreased the magnitude of the electrically induced Ca2+ transients by 30 ± 4% within 5 s. This inhibitory effect of cocaine was dose dependent, with a 50% reduction in the Ca2+ transient occurring at 40 μM cocaine. The effects of cocaine were not associated with any permanent cell damage and could be reversed by washing the cells free of the drug. Cytosolic Ca2+ increases in response to K+-induced depolarization of the cardiomyocytes were much less sensitive to cocaine than the electrically induced Ca2+ transients. In this respect the effects of cocaine were similar to the actions of lidocaine and tetrodotoxin but distinct from the effects of nitrendipine and verapamil. Cocaine had no effect on the caffeine-releasable Ca2+ pool in cardiomyocytes. These data demonstrate that cocaine directly inhibits the Ca2+-dependent steps of excitation-contraction coupling in heart muscle cells. Sarcolemmal Na+ channels represent a possible locus for this action of cocaine.

Original languageEnglish (US)
Pages (from-to)H50-H57
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume260
Issue number1 29-1
DOIs
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

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

Keywords

  • Calcium
  • Calcium transients
  • Heart

Fingerprint

Dive into the research topics of 'Inhibition by cocaine of excitation-contraction coupling in isolated cardiomyocytes'. Together they form a unique fingerprint.

Cite this