HERG1 channelopathies.
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.
Sanguinetti
Michael C
MC
Department of Physiology, Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, 95 South 2000 East, Salt Lake, UT 84112, USA. sanguinetti@cvrti.utah.edu
D000818:Animals; D053447:Channelopathies / Q000235:genetics*; D000072237:ERG1 Potassium Channel; D004827:Epilepsy / Q000235:genetics; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics; D015854:Up-Regulation
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C000606915:Kcnh2 protein, mouse