Referenced in: none

Automatically associated channels: Kir6.2

Title: Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice.

Authors: Masashi Suzuki, Tomoaki Saito, Toshiaki Sato, Masaji Tamagawa, Takashi Miki, Susumu Seino, Haruaki Nakaya

Journal, date & volume: Circulation, 2003 Feb 11 , 107, 682-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12578868

Abstract
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.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.Diazoxide enhances action potential shortening during ischemia by activating sarcK(ATP) channels and provides cardioprotection in mouse hearts.