Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects

作者：Yangyang Lin, Sam Z. Grinter, Zhongju Lu, Xianjin Xu, Hong-Zhan Wang, Hongwu Liang, Panpan Hou, Junyuan Gao, Chris Clausen, Jingyi Shi, Wenshan Zhao, Zhiwei Ma, Yongfeng Liu, Kelli McFarland White, Lu Zhao, Po Wei Kang, Guohui Zhang, Ira S. Cohen, Xiaoqin Zou, Jianmin Cui · 发表于：Proceedings of the National Academy of Sciences · 年份：2021 · DOI：10.1073/pnas.2024215118 · 被引用次数：11 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、Electrochemical Analysis and Applications

Significance C28, a chemical compound identified by computational screening, selectively facilitates voltage-dependent activation of a cardiac potassium ion channel, I Ks . This compound reverses drug-induced prolongation of the electric signals across the cardiac cell membrane known as action potentials (APs) but minimally affects the normal AP at the same dosage. This outcome supports a computational prediction that enhancing voltage-dependent activation of I Ks could be a potential therapy for AP prolongation. This therapy would increase the safety and expand the therapeutic efficacy of many currently approved drugs that induce AP prolongation, which can trigger life-threatening cardiac arrhythmias.