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

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 laevis oocytes 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.

Original languageEnglish (US)
Article numbere53901
JournaleLife
Volume9
DOIs
StatePublished - Feb 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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