The Association of Endoplasmic Reticulum Stress Response and Clearance Pathways
with Trafficking Deficiency of HERG Mutation and Pharmacological Rescue

Lian JF

Abstract

The Association of Endoplasmic Reticulum Stress Response and Clearance Pathways with Trafficking Deficiency of HERG Mutation and Pharmacological Rescue

Lian JF

The rapid activating delayed rectifier K-current (Ikr) plays a crucial role in the phase 3 repolarization of action potential of human myocardial cells. The Ikr channel is composed by the αsubunits which encoded by the human ether-a-go-go related gene (HERG). HERG mutation with Ikr channel current reduction leads to type II hereditary long QT syndrome, which is characterized by a prolonged QT interval, an abnormal T wave on the electrocardiogram (ECG), a high risk of syncope, and sudden cardiac death due to underlyinglife-threatening torsade de pointes (Tdp) arrhythmias, particularly in young patients . There are several hundred HERG mutations having been identified, with majority causing LQT2 due to trafficking deficiency of HERG proteins