title: Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice.
abstract: BACKGROUND
  We recently demonstrated that the sarcolemmal ATP-sensitive potassium (sarcK(ATP)) channel plays a key role in cardioprotection against ischemia/reperfusion injuries in Kir6.2-knockout (KO) mice. In the present study, we evaluated the effects of diazoxide, a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener, on ischemia-induced myocardial stunning in sarcK(ATP) channel-deficient mice.
  
  
  RESULTS
  Langendorff-perfused hearts of wild-type (WT) and KO mice were subjected to global ischemia/reperfusion. Diazoxide improved the recovery of contractile function in WT hearts but not in KO hearts. Treatment with HMR1098 (a sarcK(ATP) channel blocker) but not 5-hydroxydecanoate (a mitoK(ATP) channel blocker) abolished the cardioprotective effect of diazoxide in WT hearts. In coronary-perfused WT ventricular muscle preparations, action potential shortening during ischemia was accelerated in the presence of diazoxide.
  
  
  CONCLUSIONS
  Diazoxide enhances action potential shortening during ischemia by activating sarcK(ATP) channels and provides cardioprotection in mouse hearts.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Saito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sato
authors.forename: Masaji
authors.initials: M
authors.lastname: Tamagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Susumu
authors.initials: S
authors.lastname: Seino
authors.forename: Haruaki
authors.initials: H
authors.lastname: Nakaya
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics; D020127:Recovery of Function / Q000187:drug effects; D012508:Sarcolemma / Q000378:metabolism*
chemical_list: D001549:Benzamides; D002316:Cardiotonic Agents; D008565:Membrane Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C117780:mitochondrial K(ATP) channel; D000255:Adenosine Triphosphate; C410297:HMR 1098; D003981:Diazoxide