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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2017-04-01
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doaj-aa9eaae167e54e05a1324806f6e5d7a12020-12-08T01:06:30ZengNature Publishing GroupScientific Reports2045-23222017-04-017111110.1038/s41598-017-01056-0Inhibition of late sodium current suppresses calcium-related ventricular arrhythmias by reducing the phosphorylation of CaMK-II and sodium channel expressionsXiao-Hong Wei0Shan-Dong Yu1Lu Ren2Si-Hui Huang3Qiao-Mei Yang4Ping Wang5Yan-Peng Chu6Wei Yang7Yan-Sheng Ding8Yong Huo9Lin Wu10Department of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalDepartment of Cardiology, Peking University First HospitalAbstract 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+]ihttps://doi.org/10.1038/s41598-017-01056-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-04-01 |
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 |
url |
https://doi.org/10.1038/s41598-017-01056-0 |
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