Referenced in: none

Automatically associated channels: Kv11.1 , Kv7.1

Title: Identification and functional characterization of the human ether-a-go-go-related gene Q738X mutant associated with hereditary long QT syndrome type 2.

Authors: Sheng-Na Han, Song-Hua Yang, Yu Zhang, Xiao-Yan Sun, Yan-Yan Duan, Xiang-Jie Hu, Tian-Li Fan, Chen-Zheng Huang, Ge Yang, Zhao Zhang, Lirong Zhang

Journal, date & volume: Int. J. Mol. Med., 2014 Sep , 34, 810-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24993425

Abstract
QT interval prolongation, a risk factor for arrhythmias, may be associated with genetic variants in genes governing cardiac repolarization. Long QT syndrome type 2 (LQT2) is caused by mutations in the human ether-a-go‑go-related gene (hERG). This gene encodes a voltage-gated potassium channel comprised of 4 subunits, and the formation of functional channels requires the proper assembly of these 4 subunits. In the present study, we investigated the role of the LQT2 mutation, Q738X, which causes truncation of the C-terminus of hERG channels, in the assembly and function of hERG channels. When expressed in HEK293 cells, Q738X did not generate an hERG current. The co-expression of Q738X with wild-type (WT)-hERG did not cause the dominant-negative suppression of the WT-hERG current. Western blot analysis and confocal microscopy revealed that the Q738X mutation caused defective trafficking of hERG channel proteins. Co-immunoprecipitation demonstrated that Q738X did not exhibit dominant-negative effects due to the failure of the mutant and WT subunits to co-assemble. In conclusion, the functional loss caused by the Q738X mutation in hERG K+ channels may be attributed to the disruption of tetrameric assembly.