文章基本信息

标题：Coupling stabilizers open KV1-type potassium channels
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作者：Malin Silverå Ejneby ; Björn Wallner ; Fredrik Elinder 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：43
页码：27016-27021
DOI：10.1073/pnas.2007965117
出版社：The National Academy of Sciences of the United States of America
摘要：The opening and closing of voltage-gated ion channels are regulated by voltage sensors coupled to a gate that controls the ion flux across the cellular membrane. Modulation of any part of gating constitutes an entry point for pharmacologically regulating channel function. Here, we report on the discovery of a large family of warfarin-like compounds that open the two voltage-gated type 1 potassium (K V 1) channels K V 1.5 and Shaker, but not the related K V 2-, K V 4-, or K V 7-type channels. These negatively charged compounds bind in the open state to positively charged arginines and lysines between the intracellular ends of the voltage-sensor domains and the pore domain. This mechanism of action resembles that of endogenous channel-opening lipids and opens up an avenue for the development of ion-channel modulators.
关键词：potassium-channel openers ; VSD-to-pore coupling ; K v 1 channel