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

Author

Suzuki M, Saito T, Sato T, Tamagawa M, Miki T, Seino S, and Nakaya H

Subjects
Action Potentials drug effects, Adenosine Triphosphate metabolism, Animals, Benzamides pharmacology, In Vitro Techniques, Membrane Proteins drug effects, Membrane Proteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Heart drug effects, Myocardial Contraction drug effects, Myocardial Ischemia complications, Myocardial Ischemia physiopathology, Myocardial Reperfusion, Myocardial Stunning etiology, Myocardial Stunning physiopathology, Potassium Channel Blockers pharmacology, Potassium Channels deficiency, Potassium Channels drug effects, Potassium Channels genetics, Potassium Channels, Inwardly Rectifying deficiency, Potassium Channels, Inwardly Rectifying genetics, Recovery of Function drug effects, Cardiotonic Agents pharmacology, Diazoxide pharmacology, Mitochondria, Heart metabolism, Myocardial Stunning drug therapy, Potassium Channels metabolism, Sarcolemma metabolism
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., Methods and 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.

Published
2003
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