Human ether-à-go-go-related gene potassium channel (KCNH2) (hERG potassium channel (Kv11.1))

The human ether-à-go-go-related gene potassium channel (hERG, KCNH2, Kv11.1) conducts the rapid component of the delayed rectifier potassium current (IKr) essential for the repolarization of cardiac action potentials[5][7][4]. Structurally, it comprises pore-forming subunits that assemble as homo- or heterotetramers with unique gating and inactivation kinetics[4][7]. The channel is a critical therapeutic target because its inhibition, either by genetic mutation or by drugs, leads to long QT syndrome, predisposing patients to dangerous arrhythmias such as Torsades de Pointes and sudden cardiac death[5][8]. While moderate channel blockade can be antiarrhythmic, unintentional antagonism is a major safety concern for drug development, and many non-cardiac drugs have been withdrawn or restricted due to hERG liability[5][8]. The QT interval on ECG and KCNH2 genotyping are important biomarkers for patient selection and safety monitoring. The challenge for therapy is to balance antiarrhythmic efficacy without causing proarrhythmia, making safety and selectivity of utmost importance in any hERG-modulating drug.

Other names

hERGKv11.1KCNH2IKr channelether-à-go-go-related gene potassium channelrapid delayed rectifier potassium channel

Blockade of hERG/IKr potassium current (prolongs cardiac action potential duration, increases QT interval) Risk of arrhythmia via reduction of repolarizing current