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

Peter A. Brady, Shuichen Zhang, José R. López, Aleksandar Jovanovic, Alexey E. Alekseev, Andre Terzic

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)343-349
Number of pages7
JournalEuropean Journal of Pharmacology
Volume308
Issue number3
DOIs
StatePublished - Jul 25 1996

Fingerprint

Glyburide
Dinitrophenols
Cardiac Myocytes
Adenosine Triphosphate
Electrophysiology
Oxidative Phosphorylation
Muscle Cells
Guinea Pigs
Pharmaceutical Preparations

Keywords

  • ATP-sensitive K channel
  • Ca, intracellular
  • Cardiac cell
  • Chemical hypoxia
  • Dinitrophenol
  • Fluo-3
  • Glyburide

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Dual effect of glyburide, an antagonist of K(ATP) channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes. / Brady, Peter A.; Zhang, Shuichen; López, José R.; Jovanovic, Aleksandar; Alekseev, Alexey E.; Terzic, Andre.

In: European Journal of Pharmacology, Vol. 308, No. 3, 25.07.1996, p. 343-349.

Research output: Contribution to journalArticle

Brady, Peter A. ; Zhang, Shuichen ; López, José R. ; Jovanovic, Aleksandar ; Alekseev, Alexey E. ; Terzic, Andre. / Dual effect of glyburide, an antagonist of K(ATP) channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes. In: European Journal of Pharmacology. 1996 ; Vol. 308, No. 3. pp. 343-349.
@article{293468007cf54d0b95354b7d9f205b4e,
title = "Dual effect of glyburide, an antagonist of K(ATP) channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes",
abstract = "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.",
keywords = "ATP-sensitive K channel, Ca, intracellular, Cardiac cell, Chemical hypoxia, Dinitrophenol, Fluo-3, Glyburide",
author = "Brady, {Peter A.} and Shuichen Zhang and L{\'o}pez, {Jos{\'e} R.} and Aleksandar Jovanovic and Alekseev, {Alexey E.} and Andre Terzic",
year = "1996",
month = "7",
day = "25",
doi = "10.1016/0014-2999(96)00327-5",
language = "English (US)",
volume = "308",
pages = "343--349",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "3",

}

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, Andre

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

UR - http://www.scopus.com/inward/record.url?scp=0030601256&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030601256&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(96)00327-5

DO - 10.1016/0014-2999(96)00327-5

M3 - Article

C2 - 8858310

AN - SCOPUS:0030601256

VL - 308

SP - 343

EP - 349

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 3

ER -