Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening

Panpan Hou, Jodene Eldstrom, Jingyi Shi, Ling Zhong, Kelli McFarland, Yuan Gao, David Fedida, Jianmin Cui

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation.

Original languageEnglish
Article number1730
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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