Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII

Kamada, Rui; Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Watanabe, Masaya; Mizukami, Kazuya; Tenma, Taro; Takahashi, Masayuki; Takada, Shingo; Anzai, Toshihisa

Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII

Kamada, Rui; Yokoshiki, Hisashi; Mitsuyama, Hirofumi et al.

European journal of pharmacology, 2019, 844, 110-117

Permalink : https://hdl.handle.net/2115/76694

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アクセス権	open access
URI	https://hdl.handle.net/2115/76694
タイトル	Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy : The role of small-conductance calcium-activated potassium channels via activation of CaMKII
著者	Kamada, Rui ; Yokoshiki, Hisashi ; Mitsuyama, Hirofumi ; Watanabe, Masaya ; Mizukami, Kazuya ; Tenma, Taro ; Takahashi, Masayuki ; Takada, Shingo ; Anzai, Toshihisa
e-Rad_Researcher 60836104 著者名 Kamada, Rui
e-Rad_Researcher 40360911 著者名 Yokoshiki, Hisashi
著者名 Mitsuyama, Hirofumi
e-Rad_Researcher 40632047 著者名 Watanabe, Masaya
著者名 Mizukami, Kazuya
e-Rad_Researcher 00801614 著者名 Tenma, Taro
著者名 Takahashi, Masayuki
e-Rad_Researcher 60722329 著者名 Takada, Shingo
e-Rad_Researcher 60232089 著者名 Anzai, Toshihisa
言語	英語
キーワード	SK channels
	β- adrenoreceptor stimulation
	CaMKII
	Cardiac hypertrophy
	Rat
発行日	2019-02-05
出版者	Elsevier
収録物名	European journal of pharmacology
巻(号)	844
ページ	110-117
抄録	Sustained ventricular arrhythmias (SVAs) lead to sudden cardiac death, for which β- adrenoreceptor blockers are effective. We hypothesized that electrophysiological changes and arrhythmias by β- adrenoreceptor stimulation are crucially related to activation of small-conductance calcium-activated potassium (SK) channels via the increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. We used normotensive Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHRs). The latter served as a model of left ventricular hypertrophy. We performed dual optical mapping of action potentials and Ca2+ transients, and the effects of isoproterenol and apamin, an SK channel blocker, were evaluated in the Langendorff-perfused hearts. Action potential duration was abbreviated by isoproterenol (100 nM) in both WKY rats and SHRs. In contrast, the CaMKII activity was increased by isoproterenol only in SHRs. In the presence of isoproterenol, apamin prolonged the action potential duration only in SHRs (n = 10, from 116.6 ± 5.05 ms to 125.4 ± 3.80 ms, P = 0.011), which was prevented by KN-93, a CaMKII inhibitor. Increase in Ca2+ transients and shortening of Ca2+ transient duration by isoproterenol were similarly observed in both animals, which was not affected by apamin. Apamin reduced the isoproterenol-induced SVAs and maximal slope of action potential duration restitution curve specifically in SHRs. In conclusion, β- adrenoreceptor stimulation creates arrhythmogenic substrates via the CaMKII-dependent activation of SK channels in cardiac hypertrophy.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0014-2999
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ejphar.2018.12.011