HERG1 channelopathies

• Published in: Pflügers Archiv Vol. 460; no. 2; pp. 265 - 276
• Main Author: Sanguinetti, Michael C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2010; Springer Nature B.V
• Subjects: Animals; Arrhythmia; Biomedical and Life Sciences; Biomedicine; Cell Biology; Channelopathies - genetics; Channels; Epilepsy - genetics; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - chemistry; Ether-A-Go-Go Potassium Channels - genetics; Ether-A-Go-Go Potassium Channels - physiology; Ethers; Genes; Human Physiology; Humans; Ion Channels; Long QT Syndrome - genetics; Long QT Syndrome - physiopathology; Mice; Molecular Medicine; Muscular Atrophy - genetics; Mutations; Neurosciences; Physiology; Receptors; Receptors and Transporters; Risk; Up-Regulation; channel; K; Ether-à-go-go; Cardiac potassium current; Cardiac electrophysiology; Ventricular fibrillation
• ISSN: 0031-6768; 1432-2013; 1432-2013
• DOI: 10.1007/s00424-009-0758-8

Human ether a go-go-related gene type 1 (hERG1) K + channels conduct the rapid delayed rectifier K + current and mediate action potential repolarization in the heart. Mutations in KCNH2 (the gene that encodes hERG1) causes LQT2, one of the most common forms of long QT syndrome, a disorder of cardiac repolarization that predisposes affected subjects to ventricular arrhythmia and increases the risk of sudden cardiac death. Hundreds of LQT2-associated mutations have been described, and most cause a loss of function by disrupting subunit folding, assembly, or trafficking of the channel to the cell surface. Loss-of-function mutations in hERG1 channels have also recently been implicated in epilepsy. A single gain-of-function mutation has been described that causes short QT syndrome and cardiac arrhythmia. In addition, up-regulation of hERG1 channel expression has been demonstrated in specific tumors and has been associated with skeletal muscle atrophy in mice.