ナカニシ　トシオ   NAKANISHI Toshio   中西　敏雄    所属   医学部 医学科（東京女子医科大学病院）    職種   特任教授
言語種別	英語
発表タイトル	Naturally Occurring L138Q Mutation in the Voltage-gated Potassium Channel 1.5 Impairs the Channel Activity
会議名	The 75th Annual Scientific Meeting of the Japanese Circulation Society
学会区分	全国規模の学会
発表形式	ポスター掲示
講演区分	一般
発表者・共同発表者	◎Hayama Emiko, Nakanishi Toshio
発表年月日	2011/08/04
開催地 （都市, 国名）	Yokohama
概要	[Background] Voltage-gated potassium channel (Kv) 1.5 is one of important Kv channel family that are expressed in intercalated discs of atrial and ventricular myocytes, and pulmonary artery smooth muscle cells. Kv1.5 (KCNA5) loss-of-function mutation (E375X) had been determined as one of risk factors for atrial fibrillation (AF). We examined naturally occurring KCNA5 mutants on interaction with accessory Kv beta1 and the channel activity. [Methods] Twentytwo KCNA5 missense SNPs (G31V, E33V, P73S, R87Q, P91L, V115A, L138Q, G182R, L185M, E211D, R214G, P228S, S248P, A251T, A251G, P307S, P310L, V341E, P532L, R554Q, G568V, and R578K) and a nonsense mutation (E375X) were created by site-directed mutagenesis. Extracts from the HEK-293 cells expressed with wild-type or the mutant Kv1.5 with or without Kv beta1.2 are subjected to Western blotting analyses. The Kv1.5 channel activity in the HEK-293 cells was recorded using the whole-cell patch-clamp technique. [Results and conclusion] All wild-type and mutant Kv1.5 channel proteins expressed in HEK293 cells were confirmed on Western blots. Heterologously expressed L138Q and E375X mutations failed to generate the Kv1.5 current, but secure tetrameric subunit assembly. Both mutants lost interaction activity with Kv beta1.2. Since pathogenic link between loss-of-function of Kv1.5 and susceptibility to AF was reported, naturally occurring loss-of-function L138Q mutation might be a novel risk factor for AF.