Functional and pharmacological characterization of an S5 domain hERG mutation associated with short QT syndrome.

ABSTRACT: Congenital short QT syndrome (SQTS) is a repolarization disorder characterized by abbreviated QT intervals, atrial and ventricular arrhythmias and a risk of sudden death. This study characterized a missense mutation (I560T) in the S5 domain of the hERG K⁺ channel that has been associated with variant 1 of the SQTS. Whole cell patch clamp recordings of wild-type (WT) and I560T hERG current (I_hERG) were made at 37 °C from hERG expressing HEK 293 cells, and the structural context of the mutation was investigated using a recently reported cryo-EM structure of hERG. Under conventional voltage clamp, the I560T mutation increased I_hERG amplitude without altering the voltage-dependence of activation, although it accelerated activation time-course and also slowed de

SUBMITTER: Butler A 

PROVIDER: S-EPMC6479114 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature