Serine mutation of a conserved threonine in the hERG K⁺ channel S6-pore region leads to loss-of-function through trafficking impairment.

ABSTRACT: The human Ether-à-go-go Related Gene (hERG) encodes a potassium channel responsible for the cardiac rapid delayed rectifier K⁺ current, I_Kr, which regulates ventricular repolarization. Loss-of-function hERG mutations underpin the LQT2 form of congenital long QT syndrome. This study was undertaken to elucidate the functional consequences of a variant of uncertain significance, T634S, located at a highly conserved position at the top of the S6 helix of the hERG channel. Whole-cell patch-clamp recordings were made at 37 °C of hERG current (I_hERG) from HEK 293 cells expressing wild-type (WT) hERG, WT+T634S and hERG-T634S alone. When the T634S mutation was expressed alone little or no I_hERG could be recorded. Co-expressing WT and hERG-T634S suppressed

SUBMITTER: Al-Moubarak E 

PROVIDER: S-EPMC7237882 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature