Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes.
Whether sulfonylurea therapy, which blocks ATP-sensitive K+ (KATP) 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 KATP channel activity, was measured in 2-4-dinitrophenol-treated guinea-pig cardiomyocytes, using epifluorescent digital-imaging and cell-attached patch-clamp electrophysiology. Dinitrophenol (200 microM), which uncouples oxidative phosphorylation, induced opening of KATP channels and Ca2+ loading. Glyburide (6 microM) which reduced the opening of KATP channels, aggravated Ca2+ loading only when applied to dinitrophenol-pretreated myocytes but not when applied with dinitrophenol treatment. We conclude that a blocker of KATP channels has differential effects upon dinitrophenol-induced intracellular Ca2+ loading, which appear to depend upon the stage of metabolic insult.
Brady
P A
PA
Department of Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
Zhang
S
S
López
J R
JR
Jovanovic
A
A
Alekseev
A E
AE
Terzic
A
A
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers
D026902:Potassium Channel Blockers; D019297:2,4-Dinitrophenol; D005905:Glyburide; D002118:Calcium