Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions

Abstract Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90)...

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Autores principales:	Xiao-Hong Wei, Shan-Dong Yu, Lu Ren, Si-Hui Huang, Qiao-Mei Yang, Ping Wang, Yan-Peng Chu, Wei Yang, Yan-Sheng Ding, Yong Huo, Lin Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa9eaae167e54e05a1324806f6e5d7a1
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spelling	oai:doaj.org-article:aa9eaae167e54e05a1324806f6e5d7a12021-12-02T11:52:42ZInhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions10.1038/s41598-017-01056-02045-2322https://doaj.org/article/aa9eaae167e54e05a1324806f6e5d7a12017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01056-0https://doaj.org/toc/2045-2322Abstract Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration ([Ca2+]i) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone. The prolongations caused by Bay K 8644 and frequent episodes of ventricular tachycardias, both in absence and presence of ATX-II, were significantly attenuated or abolished by late I Na inhibitors TTX and eleclazine. In rabbit ventricular myocytes, Bay K 8644 increased I CaL density, calcium transient and myocyte contraction. TTX and eleclazine decreased the amplitude of late I Na, the reverse use dependence of MAPD90 at slower heart rate, and attenuated the increase of intracellular calcium transient and myocyte contraction. TTX diminished the phosphorylation of CaMKII-δ and Nav 1.5 in hearts treated with Bay K 8644 and ATX-II. In conclusion, late I Na contributes to ventricular arrhythmias and its inhibition is plausible to treat arrhythmias in hearts with increased [Ca2+]iXiao-Hong WeiShan-Dong YuLu RenSi-Hui HuangQiao-Mei YangPing WangYan-Peng ChuWei YangYan-Sheng DingYong HuoLin WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiao-Hong Wei Shan-Dong Yu Lu Ren Si-Hui Huang Qiao-Mei Yang Ping Wang Yan-Peng Chu Wei Yang Yan-Sheng Ding Yong Huo Lin Wu Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
description	Abstract Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration ([Ca2+]i) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone. The prolongations caused by Bay K 8644 and frequent episodes of ventricular tachycardias, both in absence and presence of ATX-II, were significantly attenuated or abolished by late I Na inhibitors TTX and eleclazine. In rabbit ventricular myocytes, Bay K 8644 increased I CaL density, calcium transient and myocyte contraction. TTX and eleclazine decreased the amplitude of late I Na, the reverse use dependence of MAPD90 at slower heart rate, and attenuated the increase of intracellular calcium transient and myocyte contraction. TTX diminished the phosphorylation of CaMKII-δ and Nav 1.5 in hearts treated with Bay K 8644 and ATX-II. In conclusion, late I Na contributes to ventricular arrhythmias and its inhibition is plausible to treat arrhythmias in hearts with increased [Ca2+]i
format	article
author	Xiao-Hong Wei Shan-Dong Yu Lu Ren Si-Hui Huang Qiao-Mei Yang Ping Wang Yan-Peng Chu Wei Yang Yan-Sheng Ding Yong Huo Lin Wu
author_facet	Xiao-Hong Wei Shan-Dong Yu Lu Ren Si-Hui Huang Qiao-Mei Yang Ping Wang Yan-Peng Chu Wei Yang Yan-Sheng Ding Yong Huo Lin Wu
author_sort	Xiao-Hong Wei
title	Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
title_short	Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
title_full	Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
title_fullStr	Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
title_full_unstemmed	Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions
title_sort	inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of camk-ii and sodium channel expressions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/aa9eaae167e54e05a1324806f6e5d7a1
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Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressions

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