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フルテキストURLA050058000101.pdf ( 1.5MB ) 公開日 2011-12-19
タイトルDefective conformational regulation of the ryanodine receptor as a key pathogenic mechanism of catecholaminergic polymorphic ventricular tachycardia
作成者Uchinoumi, Hitoshi
Yano, Masafumi
Matsuzaki, Masunori
作成者ヨミウチノウミ, ヒトシ
ヤノ, マサフミ
マツザキ, マスノリ
作成者別表記内海, 仁志
矢野, 雅文
松﨑, 益徳
作成者所属山口大学医学部附属病院
山口大学大学院医学系研究科(医学)
内容記述(抄録等)Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease occurring in patients with a structurally normal heart: the disease is characterized by life-threatening arrhythmias elicited by stress and emotion. CPVT is known to be caused by a mutation-linked channel disorder in the cardiac ryanodine receptor (RyR2). However, the underlying mechanism by which a single mutation in such a large molecule produces drastic effects on channel function remains unresolved. The unique distribution of these mutation sites has led to the concept that interaction among the putative regulatory domains within the RyR has a key role in regulating channel opening. Here, we report that introduction of R2474S CPVT mutation into the central domain of mouse RyR2 interfered with a normal tight interaction between the central domain (aa 2000–2500) and the N-terminal domain (aa 1-600), which reduced the threshold of luminal [Ca^<2+>] for channel activation, sensitized to the protein kinase A-dependent phosphorylation, and in turn led to CPVT.
本文言語eng
著者キーワードryanodine receptor
calcium
ventricular tachycardia
sarcoplasmic reticulum
資料タイプtext
ファイル形式application/pdf
出版者Yamaguchi University School of Medicine
NII資料タイプ紀要論文
学内刊行物(紀要等)The bulletin of the Yamaguchi Medical School
掲載誌名The bulletin of the Yamaguchi Medical School
58
1-2
開始ページ1
終了ページ5
発行日2011
著者版/出版社版出版社版
リポジトリIDA050058000101
地域区分山口大学
URIhttp://www.lib.yamaguchi-u.ac.jp/yunoca/handle/A050058000101