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

Elrod JW, Harrell M, Flagg TP, Gundewar S, Magnuson MA, Nichols CG, Coetzee WA, Lefer DJ
Circulation. 2008 117 (11): 1405-13

PMID: 18316485 · DOI:10.1161/CIRCULATIONAHA.107.745539

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.

MeSH Terms (20)

Animals ATP-Binding Cassette Transporters Diabetes Complications Fibrosis Hypoglycemic Agents KATP Channels Mice Mice, Knockout Multidrug Resistance-Associated Proteins Myocardial Infarction Myocardial Reperfusion Injury Myocarditis Myocytes, Cardiac Patch-Clamp Techniques Potassium Channels Potassium Channels, Inwardly Rectifying Receptors, Drug Sulfonylurea Compounds Sulfonylurea Receptors Ventricular Dysfunction, Left

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