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

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 mu M), which uncouples oxidative phosphorylation, induced opening of K-ATP channels and Ca2+ loading. Glyburide (6 mu M) 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.