TY - JOUR
T1 - Dual effect of glyburide, an antagonist of K(ATP) channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes
AU - Brady, Peter A.
AU - Zhang, Shuichen
AU - López, José R.
AU - Jovanovic, Aleksandar
AU - Alekseev, Alexey E.
AU - Terzic, André
N1 - Funding Information:
This work was supported by grants to A.T. from the American Heart Association, and the National Heart Foundation, a program of the American Health Assistance Foundation. A.T. is a recipient of the Ruth Salta Young Investigator Award from the National Heart Foundation and of the Faculty Developmental Award from the Pharmaceutical Research and Manufacturers of America Foundation. P.A.B. is a recipient of the General Mills Foundation Clinician-Investigator Fellowship Award.
PY - 1996/7/25
Y1 - 1996/7/25
N2 - 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.
AB - 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.
KW - ATP-sensitive K channel
KW - Ca, intracellular
KW - Cardiac cell
KW - Chemical hypoxia
KW - Dinitrophenol
KW - Fluo-3
KW - Glyburide
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U2 - 10.1016/0014-2999(96)00327-5
DO - 10.1016/0014-2999(96)00327-5
M3 - Article
C2 - 8858310
AN - SCOPUS:0030601256
SN - 0014-2999
VL - 308
SP - 343
EP - 349
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -