Yasunori Ishii (1,2), Katsuhiko Muraki (1), Atsushi Kurihara (2), Yuji Imaizumi (1,*) and Minoru Watanabe (1)
(1) Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabedori, Mizuho-ku, Nagoya 467, Japan (2) Biology Section, Shirakawa Laboratory, Nippon Roussel Co., Ltd., 103-1 Ushishimizu, Shirakawa, Fukushima 961, Japan (*) To whom correspondence should be addressed.
Abstract: Effects of sematilide, a novel class III antiarrhythmic agent, on the delayed rectifier K+ current (IK) were examined in guinea pig atrial myocytes using a voltage clamp technique. Sematilide inhibited both time-dependent outward current upon depolarization and tail currents (IK-tail) at -40 mV. The concentration of sematilide required for a 50% decrease in IK-tail was approximately 50 microM. The sematilide- sensitive current obtained using a triangular voltage command exhibited marked inward rectification and had the maximum amplitude at -30 mV. These results suggest that sematilide inhibits rapidly activating IK in guinea pig atrial myocytes, resulting in the prolongation of action potential duration and refractoriness.
Keywords:
Sematilide, Delayed rectifier K+ current, Guinea pig atrium