Potassium channel subunit Kv11.1 (hERG)

Potassium channel subunit Kv11.1 (hERG) is a voltage-gated potassium channel encoded by the KCNH2 gene. It forms the pore-forming alpha subunit of the channel responsible for the rapid delayed rectifier K(+) current (I_Kr_) in cardiac cells and plays a pivotal role in repolarizing the cardiac action potential, thereby determining the duration of the cardiac QT interval on the ECG[1][2][5][7]. Structurally, hERG consists of six transmembrane domains per subunit (S1–S6), a prominent voltage sensor, and unique cytoplasmic PAS and cyclic nucleotide-binding domains, forming functional tetramers[5][6]. Its high sensitivity to blockade by a wide variety of drugs is a longstanding challenge in pharmaceutical safety, as such inhibition can lead to life-threatening arrhythmias and has resulted in market withdrawal or restriction of numerous drugs[2][7]. Inherited or acquired loss/gain of function of hERG leads to syndromes associated with abnormal cardiac repolarization, including long and short QT syndromes, with critical implications for arrhythmogenesis and sudden cardiac death[1][7]. The channel’s kinetics and pharmacology remain major subjects of cardiovascular, pharmacological, and drug safety research[1][2][4][5][7].

Other names

Human ether-à-go-go-related gene productPotassium voltage-gated channel subfamily H member 2KCNH2Ether-à-go-go potassium channelERG1

Blockers: Many drugs act as hERG channel blockers, inhibiting the rapid delayed rectifier K(+) current (I_Kr_), leading to prolonged ventricular repolarization and QT interval[1][2][5][7]. Gain/loss of function by genetic mutation modifies channel inactivation and repolarization dynamics[1][5].