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(Circulation. 2008;117:1405-1413.)
© 2008 American Heart Association, Inc.

Molecular Cardiology

Role of Sulfonylurea Receptor Type 1 Subunits of ATP-Sensitive Potassium Channels in Myocardial Ischemia/Reperfusion Injury

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

From the Department of Medicine and Pathology (J.W.E., S.G., D.J.L.), Albert Einstein College of Medicine, New York, NY; Department of Pediatrics (M.H., W.A.C.), NYU School of Medicine, New York, NY; Department of Cell Biology and Physiology (T.P.F., C.G.N.), Washington University School of Medicine, St Louis, Mo; and Department of Molecular Physiology and Biophysics (M.A.M.), Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dr William A. Coetzee, Pediatric Cardiology, NYU School of Medicine, 560 First Ave, TCH-521, New York, NY 10016. E-mail william.coetzee{at}med.nyu.edu

Received October 11, 2007; accepted January 22, 2008.

Background— Opening of cardiac ATP-sensitive potassium channels (K_ATP channels) is a well-characterized protective mechanism against ischemia and reperfusion injury. Evidence exists for an involvement of both sarcolemmal and mitochondrial K_ATP channels in such protection. Classically, cardiac sarcolemmal K_ATP 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 K_ATP channel subunit in cardiovascular function during conditions of stress.

Conclusions— SUR1 subunits have a high sensitivity toward many sulfonylureas and certain K_ATP 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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 117: 1353. [Full Text]