Dual effect of glyburide, an antagonist of K(ATP) channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes

Peter A. Brady, Shuichen Zhang, José R. López, Aleksandar Jovanovic, Alexey E. Alekseev, André Terzic

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Whether sulfonylurea therapy, which blocks ATP-sensitive K+ (K(ATP)) channels, impedes endogenous cardioprotective mechanisms during cellular metabolic impairment remains controversial. Therefore, the effect of glyburide, a prototype sulphonylurea drug, on cytosolic Ca2+ concentration and K(ATP) channel activity, was measured in 2-4-dinitrophenol-treated guinea-pig cardiomyocytes, using epifluorescent digital-imaging and cell-attached patch-clamp electrophysiology. Dinitrophenol (200 μM), which uncouples oxidative phosphorylation, induced opening of K(ATP) channels and Ca2+ loading. Glyburide (6 μM) which reduced the opening of K(ATP) channels, aggravated Ca2+ loading only when applied to dinitrophenol-pretreated myocytes but not when applied with dinitrophenol treatment. We conclude that a blocker of K(ATP) channels has differential effects upon dinitrophenol-induced intracellular Ca2+ loading, which appear to depend upon the stage of metabolic insult.

Original languageEnglish (US)
Pages (from-to)343-349
Number of pages7
JournalEuropean Journal of Pharmacology
Volume308
Issue number3
DOIs
StatePublished - Jul 25 1996
Externally publishedYes

Keywords

  • ATP-sensitive K channel
  • Ca, intracellular
  • Cardiac cell
  • Chemical hypoxia
  • Dinitrophenol
  • Fluo-3
  • Glyburide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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