Kaori Hamada (#), Jun Yamazaki and Taku Nagao
Laboratory of Pharmacology and Toxicology Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan
(#) Present address for correspondence: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3, Tokodai, Tsukuba 300-26, Japan
Abstract: The elevation of the myocardial extracellular potassium concentration ([K+]o) is known to shorten action potential duration, which may lead to the occurrence of arrhythmias. The aim of this study was to compare the mechanisms responsible for the shortening of monophasic action potential duration (MAPD) in hyperkalemic and myocardial ischemic hearts in anesthetized dogs. During a venous infusion of KCI for 5 min, [K+]o was increased and MAPD was significantly shortened. The ATP-sensitive K+ (KATP) channel blocker glibenclamide did not affect the shortening of MAPD during KCI-infusion, indicating that KATP channels are not involved in this mechanism. During 5-min occlusion of the left anterior descending coronary artery, [K+]o was increased, myocardial pH was decreased and MAPD was shortened. Glibenclamide completely abolished the shortening of MAPD, while partial elevation of [K+]o remained even in the presence of glibenclamide. This suggests that the shortening of MAPD is dependent mainly on the activation of KATP channels. Both models in the present study demonstrate that different types of potassium channels are involved in the regulation of action potential duration.
Keywords: Extracellular potassium, Ischemia, ATP-sensitive potassium channel, Monophasic action potential duration