Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury

John W. Elrod, Maddison Harrell, Thomas P. Flagg, Susheel Gundewar, Mark A. Magnuson, Colin G. Nichols, William A. Coetzee, David J. Lefer

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

BACKGROUND - Opening of cardiac ATP-sensitive potassium channels (KATP channels) is a well-characterized protective mechanism against ischemia and reperfusion injury. Evidence exists for an involvement of both sarcolemmal and mitochondrial KATP channels in such protection. Classically, cardiac sarcolemmal KATP channels are thought to be composed of Kir6.2 (inward-rectifier potassium channel 6.2) and SUR2A (sulfonylurea receptor type 2A) subunits; however, the evidence is strong that SUR1 (sulfonylurea receptor type 1) subunits are also expressed in the heart and that they may have a functional role. The aim of this study, therefore, was to examine the role of SUR1 in myocardial infarction. METHODS AND RESULTS - We subjected mice lacking SUR1 subunits to in vivo myocardial ischemia/reperfusion injury. Interestingly, the SUR1-null mice were markedly protected against the ischemic insult, displaying a reduced infarct size and preservation of left ventricular function, which suggests a role for this KATP channel subunit in cardiovascular function during conditions of stress. CONCLUSIONS - SUR1 subunits have a high sensitivity toward many sulfonylureas and certain KATP channel-opening drugs. Their potential role during ischemic events should therefore be considered both in the interpretation of experimental data with pharmacological agents and in the clinical arena when the cardiovascular outcome of patients treated with antidiabetic sulfonylureas is being considered.

Original languageEnglish
Pages (from-to)1405-1413
Number of pages9
JournalCirculation
Volume117
Issue number11
DOIs
StatePublished - Mar 1 2008

Keywords

  • Infarction
  • Ion channels
  • Ischemia
  • K channels
  • Myocardial infarction

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    Elrod, J. W., Harrell, M., Flagg, T. P., Gundewar, S., Magnuson, M. A., Nichols, C. G., Coetzee, W. A., & Lefer, D. J. (2008). Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury. Circulation, 117(11), 1405-1413. https://doi.org/10.1161/CIRCULATIONAHA.107.745539