Dual effect of sulfonylurea drugs on Ca2+ loading in hypoxic cardiac cells

P. A. Brady, S. Zhang, J. R. Lopez, A. Jovanovic, A. E. Alekseev, A. Terzic

Research output: Contribution to journalArticle

Abstract

Whether antidiabetic sulfonylurea drugs, such as glyburide, have deleterious effects upon the hypoxic myocardium through blockade of cardioprotective KATP channels remains controversial. To investigate this, the effect of glyburide on cytosolic Ca2+ concentration, an index of cell injury, and on KATP channel activity was measured using epifluorescent digital-imaging and cell-attached patch-clamp electrophysiology in a single cell model of chemical hypoxia induced by 2-4-dinitrophenol. Dinitrophenol (200 μM), which uncouples oxidativephosphorylation, induced opening of KATP channels and Ca2+ loading in ventricular guinea-pig cardiomyocytes. Glyburide (6 μM) which reduced the opening of KATP channels, aggravated Ca2+ loading only when applied to dinitrophenol-pretreated myocytes but not when applied concomitantly with dinitrophenol. We conclude that glyburide has differential effects upon dinitrophenol-induced intracellular Ca2+ loading, which appear to depend upon the stage of metabolic insult. These findings indicate that sulfonylurea-therapy may impair endogenous cardioprotective mechanisms, and that their use after the onset of myocardial ischemia can lead to accelerated cell death.

Original languageEnglish (US)
Number of pages1
JournalClinical pharmacology and therapeutics
Volume61
Issue number2
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Brady, P. A., Zhang, S., Lopez, J. R., Jovanovic, A., Alekseev, A. E., & Terzic, A. (1997). Dual effect of sulfonylurea drugs on Ca2+ loading in hypoxic cardiac cells. Clinical pharmacology and therapeutics, 61(2).