Pharmacological nNOS inhibition modified small-conductance Ca2+-activated K plus channel without altering Ca2+dynamics

Koya, Taro; Watanabe, Masaya; Natsui, Hiroyuki; Kadosaka, Takahide; Koizumi, Takuya; Nakao, Motoki; Hagiwara, Hikaru; Kamada, Rui; Temma, Taro; Anzai, Toshihisa

Pharmacological nNOS inhibition modified small-conductance Ca2+-activated K plus channel without altering Ca2+dynamics

Koya, Taro; Watanabe, Masaya; Natsui, Hiroyuki et al.

American journal of physiology. Heart and circulatory physiology, 2022, 323(5), H869-H878

Permalink : https://hdl.handle.net/2115/90688

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https://doi.org/10.1152/ajpheart.00252.2022			118

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アクセス権	open access
URI	https://hdl.handle.net/2115/90688
タイトル	Pharmacological nNOS inhibition modified small-conductance Ca2+-activated K plus channel without altering Ca2+dynamics
著者	Koya, Taro ; Watanabe, Masaya ; Natsui, Hiroyuki ; Kadosaka, Takahide ; Koizumi, Takuya ; Nakao, Motoki ; Hagiwara, Hikaru ; Kamada, Rui ; Temma, Taro ; Anzai, Toshihisa
著者名 Koya, Taro
e-Rad_Researcher 40632047 著者名 Watanabe, Masaya
著者名 Natsui, Hiroyuki
著者名 Kadosaka, Takahide
著者名 Koizumi, Takuya
著者名 Nakao, Motoki
著者名 Hagiwara, Hikaru
著者名 Kamada, Rui
著者名 Temma, Taro
e-Rad_Researcher 60232089 著者名 Anzai, Toshihisa
言語	英語
キーワード	atrial fibrillation
	neuronal nitric oxide synthase
	small-conductance Ca2+-activated K plus channel
発行日	2022-11-01
出版者	American Physiological Society
収録物名	American journal of physiology. Heart and circulatory physiology
巻(号)	323(5)
ページ	H869-H878
抄録	Atrial fibrillation (AF) is associated with electrical remodeling processes that promote a substrate for the maintenance of AF. Although the small-conductance Ca2+-activated K+ (SK) channel is a key factor in atrial electrical remodeling, the mechanism of its activation remains unclear. Regional nitric oxide (NO) production by neuronal nitric oxide synthase (nNOS) is involved in atrial electrical remodel-ing. In this study, atrial tachyarrhythmia (ATA) induction and optical mapping were performed on perfused rat hearts. nNOS is pharma-cologically inhibited by S-methylthiocitrulline (SMTC). The influence of the SK channel was examined using a specific channel inhibitor, apamin (APA). Parameters such as action potential duration (APD), conduction velocity, and calcium transient (CaT) were evaluated using voltage and calcium optical mapping. The dominant frequency was examined in the analysis of AF dynamics. SMTC (100 nM) increased the inducibility of ATA and apamin (100 nM) mitigated nNOS inhibition-induced arrhythmogenicity. SMTC caused abbrevia-tions and enhanced the spatial dispersion of APD, which was reversed by apamin. By contrast, conduction velocity and other parame-ters associated with CaT were not affected by SMTC or apamin administration. Apamin reduced the frequency of SMTC-induced ATA. In summary, nNOS inhibition abbreviates APD by modifying the SK channels. A specific SK channel blocker, apamin, mitigated APD abbreviation without alteration of CaT, implying an underlying mechanism of posttranslational modification of SK channels. NEW & NOTEWORTHY We demonstrated that pharmacological nNOS inhibition increased the atrial arrhythmia inducibility and a specific small-conductance Ca2 +-activated K+ channel blocker, apamin, reversed the enhanced atrial arrhythmia inducibility. Apamin mitigated APD abbreviation without alteration of Ca2+ transient, implying an underlying mechanism of posttranslational modification of SK channels.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	0363-6135
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1152/ajpheart.00252.2022