Selectivity filter modalities and rapid inactivation of the hERG1 channel.

ABSTRACT: The human ether-á-go-go-related gene (hERG1) channel conducts small outward K⁺ currents that are critical for cardiomyocyte membrane repolarization. The gain-of-function mutation N629D at the outer mouth of the selectivity filter (SF) disrupts inactivation and K⁺-selective transport in hERG1, leading to arrhythmogenic phenotypes associated with long-QT syndrome. Here, we combined computational electrophysiology with Markov state model analysis to investigate how SF-level gating modalities control selective cation transport in wild-type (WT) and mutant (N629D) hERG1 variants. Starting from the recently reported cryogenic electron microscopy (cryo-EM) open-state channel structure, multiple microseconds-long molecular-dynamics (MD) trajectories were generated usin

SUBMITTER: Miranda WE 

PROVIDER: S-EPMC7022143 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature