Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to chemical hypoxia-reoxygenation injury

Aleksandar Jovanović, Sofija Jovanović, Eva Lorenz, Andre Terzic

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Background Opening of cardiac ATP-sensitive K+ (K(ATP)) channels has emerged as a promising but still controversial cardioprotective mechanism. Defining K(ATP) channel function at the level of recombinant channel proteins is a necessary step toward further evaluation of the cardioprotective significance of this ion conductance. Methods and Results - K(ATP) channel- deficient COS-7 cells were found to be vulnerable to chemical hypoxia- reoxygenation injury that induced significant cytosolic Ca2+ loading (from 97±3 to 236±11 nmol/L). In these cells, the potassium channel opener pinacidil (10 μmol/L) did not prevent Ca2+ loading (from 96±3 nmol/L before to 233±12 nmol/L after reoxygenation) or evoked membrane current. Cotransfection with Kir6.2/SUR2A genes, which-encode cardiac K(ATP) channel subunits, resulted in a cellular phenotype that, in the presence of pinacidil (10 μmol/L), expressed K+ current and gained resistance to hypoxia- reoxygenation (Ca2+ concentration from 99±7 to 127±11 nmol/L; P>0.05). Both properties were abolished by the K(ATP) channel blocker glyburide (1 μmol/L). In COS-7 cells transfected with individual channel subunits Kit6.2 or SUR2A, which alone do not form functional cardiac K(ATP) channels, pinacidil did not protect against hypoxia-reoxygenation. Conclusions - The fact that transfer of cardiac K(ATP) channel subunits protected natively K(ATP) channel-deficient cells provides direct evidence that the cardiac K(ATP) channel protein complex harbors intrinsic cytoprotective properties. These findings validate the concept that targeting cardiac K(ATP) channels should be considered a valuable approach to protect the myocardium against injury.

Original languageEnglish (US)
Pages (from-to)1548-1555
Number of pages8
JournalCirculation
Volume98
Issue number15
DOIs
StatePublished - Oct 13 1998

Keywords

  • Calcium
  • Hypoxia
  • Ischemia
  • Potassium channels
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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