Back to Search Start Over

Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state

Authors :
Keenan C Taylor
Po Wei Kang
Panpan Hou
Nien-Du Yang
Georg Kuenze
Jarrod A Smith
Jingyi Shi
Hui Huang
Kelli McFarland White
Dungeng Peng
Alfred L George
Jens Meiler
Robert L McFeeters
Jianmin Cui
Charles R Sanders
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

Voltage-gated ion channels feature voltage sensor domains (VSDs) that exist in three distinct conformations during activation: resting, intermediate, and activated. Experimental determination of the structure of a potassium channel VSD in the intermediate state has previously proven elusive. Here, we report and validate the experimental three-dimensional structure of the human KCNQ1 voltage-gated potassium channel VSD in the intermediate state. We also used mutagenesis and electrophysiology in Xenopus laevisoocytes to functionally map the determinants of S4 helix motion during voltage-dependent transition from the intermediate to the activated state. Finally, the physiological relevance of the intermediate state KCNQ1 conductance is demonstrated using voltage-clamp fluorometry. This work illuminates the structure of the VSD intermediate state and demonstrates that intermediate state conductivity contributes to the unusual versatility of KCNQ1, which can function either as the slow delayed rectifier current (IKs) of the cardiac action potential or as a constitutively active epithelial leak current.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.10c6d390644901b22e9bb15828c3d3
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.53901