Cocaine-induced inhibition of ATP-sensitive K+ channels in rat ventricular myocytes and in heart-derived H9c2 cells

Sheng Nan Wu, Hang Dong Chang, Ruey J. Sung

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Cocaine use may cause coronary artery spasm and acute myocardial ischaemia/infarction. However, its effects on ATP-sensitive K+ (KATP) channel, an ion channel responsible for ischaemic preconditioning, remain unknown. In isolated rat ventricular myocytes with whole-cell experiments, cocaine can reverse action potential shortening and increased K+ current caused by the openers of ATP-sensitive K+ (KATP) channels. In inside-out patches, cocaine applied to intracellular surface suppressed KATP-channel activity in a concentration-dependent manner with an IC50 value of 9.2 μM; however, it did not modify the single-channel conductance of this channel. The change in the kinetic behaviour of KATP channels caused by cocaine is primarily the result of an increase in mean closed time and a decrease in mean open time. Cocaine-induced inhibition of KATP channels is independent of change in intracellular ATP concentrations. In heart-derived H9c2 cells, cocaine is also capable of suppressing KATP-channel activity. The present study provides evidence that cocaine can produce a depressant action on KATP channels in cardiac myocytes, and thus disturb ischaemic preconditioning in clinical settings.

Original languageEnglish
Pages (from-to)510-517
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume98
Issue number5
DOIs
Publication statusPublished - 2006 May

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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