Small-conductance Ca2+-activated K+ channel activation deteriorates hypoxic ventricular arrhythmias via CaMKII in cardiac hypertrophy

Tenma Taro; Mitsuyama Hirofumi; Watanabe Masaya; Kakutani Naoya; Otsuka Yutaro; Mizukami Kazuya; Kamada Rui; Takahashi Masayuki; Takada Shingo; Sabe Hisataka; Tsutsui Hiroyuki; Yokoshiki Hisashi

タイトル	en Small-conductance Ca2+-activated K+ channel activation deteriorates hypoxic ventricular arrhythmias via CaMKII in cardiac hypertrophy
その他のタイトル	en SK channels deteriorate hypoxic ventricular arrhythmia
作成者	en Tenma, Taro en Mitsuyama, Hirofumi en Watanabe, Masaya en Kakutani, Naoya en Otsuka, Yutaro en Mizukami, Kazuya en Kamada, Rui en Takahashi, Masayuki en Takada, Shingo NRID 1000060722329 en Sabe, Hisataka NRID 1000040187282 en Tsutsui, Hiroyuki NRID 1000070264017 en Yokoshiki, Hisashi NRID 1000040360911
アクセス権	open access
主題	Other en Ca2+/calmodulin-dependent protein kinase II (CaMKII) Other en cardiac hypertrophy Other en myocardial hypoxia Other en small-conductance Ca2+-activated K+ (SK) channels Other en ventricular arrhythmia NDC 490
内容注記	Abstract en The molecular and electrophysiological mechanisms of acute ischemic ventricular arrhythmias in hypertrophied hearts are not well known. We hypothesized that small-conductance Ca2+-activated K+ (SK) channels are activated during hypoxia via the Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs) as a model of cardiac hypertrophy. The inhibitory effects of SK channels and ATP-sensitive K+ channels on electrophysiological changes and genesis of arrhythmias during simulated global hypoxia (GH) were evaluated. Hypoxia-induced abbreviation of action potential duration (APD) occurred earlier in ventricles from SHRs versus. WKY rats. Apamin, a SK channel blocker, prevented this abbreviation in SIIRs in both the early and delayed phase of GH, whereas in WKY rats only the delayed phase was prevented. In contrast, SHRs were less sensitive to glibenclamide, a ATP-sensitive K+ channel blocker, which inhibited the APD abbreviation in both phases of GH in WKY rats. SK channel blockers (apamin and UCL-1684) reduced the incidence of hypoxia-induced sustained ventricular arrhythmias in SHRs but not in WKY rats. Among three SK channel isoforms. SK2 channels were directly coimmunoprecipitated with CaMKII phosphorylated at Thr(286) (p-CaMKII). We conclude that activation of SK channels leads to the APD abbreviation and sustained ventricular arrhythmias during simulated hypoxia, especially in hypertrophied hearts. This mechanism may result from p-CaMKII-bound SK2 channels and reveal new molecular targets to prevent lethal ventricular arrhythmias during acute hypoxia in cardiac hypertrophy. NEW & NOTEWORTHY We now show a new pathophysiological role of small-conductance Ca2+-activated K+ channels, which shorten the action potential duration and induce ventricular arrhythmias during hypoxia. We also demonstrate that small-conductance Ca2+-activated K+ channels interact with phosphorylated Ca2+/calmodulin-dependent protein kinase II at Thr(286) in hypertrophied hearts.
出版者	en American Physiological Society
日付	Issued2018-08
言語	eng
資源タイプ	journal article
出版タイプ	AM
資源識別子	HDL http://hdl.handle.net/2115/75062
関連	isVersionOf DOI https://doi.org/10.1152/ajpheart.00636.2017
収録誌情報	PISSN 0363-6135 en American journal of physiology. Heart and circulatory physiology 巻315 号2 開始ページH262 終了ページH272
ファイル	fulltext AmJPhysiol-HeartCirculPhysiol315_H262.pdf 2.49 MB (application/pdf) Issued2018-08
コンテンツ更新日時	2023-07-26