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