title: Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Brady
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: J R
authors.initials: JR
authors.lastname: López
authors.forename: A
authors.initials: A
authors.lastname: Jovanovic
authors.forename: A E
authors.initials: AE
authors.lastname: Alekseev
authors.forename: A
authors.initials: A
authors.lastname: Terzic
mesh_terms: 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
chemical_list: D026902:Potassium Channel Blockers; D019297:2,4-Dinitrophenol; D005905:Glyburide; D002118:Calcium