Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.
Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.
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DOI：
10.1038/s41598-021-91528-1
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发表时间：
2021-06-08
影响因子：
4.6
通讯作者：
Abi-Gerges N
中科院分区：
文献类型：
--
作者：
Ton AT;Nguyen W;Sweat K;Miron Y;Hernandez E;Wong T;Geft V;Macias A;Espinoza A;Truong K;Rasoul L;Stafford A;Cotta T;Mai C;Indersmitten T;Page G;Miller PE;Ghetti A;Abi-Gerges N
晚期钠电流（late INa）抑制已被提议用于抑制由病理状态产生或由药物诱导的心律失常的发生率。然而，晚期INa在人类心脏中的作用仍然知之甚少。因此，我们研究的作用，这种电导在心律失常中使用成人原代心肌细胞和组织从供体心脏。用ATX-II（槽纹海葵毒素II）和E-4031（hERG通道的选择性阻断剂）增强晚期INa可减慢动作电位复极动力学，损害Ca 2+稳态，增加收缩力，并增加心律失常标志物的表现。这些作用可被晚期INa抑制剂雷诺嗪和GS-967逆转。我们还报告了来自受房颤影响的供体心脏的心房组织在没有药物治疗的情况下表现出心律失常标志物，并且GS-967对晚期INa的抑制导致心律失常行为的显著减少。这些发现揭示了迟发性INa在心律失常中的关键作用，并表明抑制这种传导可以提供有效的治疗策略。最后，本研究强调了人类离体心脏模型在推进心脏转化科学方面的实用性。
Late sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences.
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影响因子：
120.1
作者：
Cook, David;Brown, Dearg;Pangalos, Menelas N.
通讯作者：
Pangalos, Menelas N.
影响因子：
8.4
作者：
Bos, J. Martijn;Crotti, Lia;Ackerman, Michael J.
通讯作者：
Ackerman, Michael J.
DOI：
10.1016/j.vascn.2016.03.009
发表时间：
2016-09-01
影响因子：
1.9
作者：
Crumb, William J., Jr.;Vicente, Jose;Strauss, David G.
通讯作者：
Strauss, David G.
影响因子：
37.8
作者：
Burashnikov, Alexander;Di Diego, Jose M.;Antzelevitch, Charles
通讯作者：
Antzelevitch, Charles
DOI：
10.1152/ajpheart.00071.2017
发表时间：
2018-02-01
影响因子：
4.8
作者：
El-Bizri, Nesrine;Li, Cindy Hong;Belardinelli, Luiz
通讯作者：
Belardinelli, Luiz