title: Role of sulfonylurea receptor type 1 subunits of ATP-sensitive potassium channels in myocardial ischemia/reperfusion injury.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medicine and Pathology, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Elrod
authors.forename: Maddison
authors.initials: M
authors.lastname: Harrell
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Flagg
authors.forename: Susheel
authors.initials: S
authors.lastname: Gundewar
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
authors.forename: William A
authors.initials: WA
authors.lastname: Coetzee
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D048909:Diabetes Complications / Q000503:physiopathology; D005355:Fibrosis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000503:physiopathology; D009205:Myocarditis / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000235:genetics; D011955:Receptors, Drug / Q000096:biosynthesis / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D064233:Sulfonylurea Receptors; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D054086:KATP Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577508:Abcc8 protein, mouse; C577511:Abcc9 protein, mouse; C092520:uK-ATP-1 potassium channel