Human ether-à-go-go-related gene potassium channel (Kv11.1) (hERG (also Kv11.1))

The human ether-à-go-go-related gene potassium channel (hERG/Kv11.1) is a voltage-gated ion channel encoded by the KCNH2 gene that forms the pore-forming subunit of the rapid component of the delayed rectifier potassium current (\(I_{Kr}\)) in cardiomyocytes. Structurally, it is a tetrameric protein with each subunit containing six transmembrane segments and cytoplasmic N-terminal PAS domains as well as C-terminal cyclic nucleotide binding domains. The primary physiological role of hERG channels is to mediate repolarization during phase 3 of the cardiac action potential, thus regulating heart rhythm and duration between beats. hERG channels are clinically significant because their dysfunction—either through genetic mutation or drug-induced inhibition—can lead to dangerous prolongation of ventricular repolarization manifested as long QT syndrome, predisposing individuals to potentially fatal arrhythmias such as torsades de pointes and sudden cardiac death. Many non-cardiac drugs have been withdrawn from clinical use due to unintended blockade of this target. Beyond cardiology, hERG expression has also been observed in some brain regions, smooth muscle cells, endocrine cells, and various tumor cell lines; however, its best-characterized function remains within cardiovascular physiology.[1][2][3][4][5]

Other names

hERGKv11.1KCNH2 (gene name)Rapid delayed rectifier potassium channelIKr channel

Blockade of the hERG/Kv11.1 channel inhibits the rapid component of the delayed rectifier K+ current, leading to prolonged cardiac repolarization and QT interval extension on ECG; this can increase risk for arrhythmias such as torsades de pointes[1][6].