Potassium channel protein hERG subunit alpha (hERG (also Kv11.1))

The **potassium channel protein hERG subunit alpha** is the alpha subunit of a voltage-gated potassium channel encoded by the *KCNH2* gene (also called Kv11.1). It is best known for its **critical role in cardiac action potential repolarization**, mediating the rapid delayed rectifier potassium current (I_Kr), which is essential for the timing and termination of the heart's electrical signal. Blockade or mutation of this channel can lead to potentially fatal heart rhythm disorders, most famously long QT syndrome, and many marketed drugs have been withdrawn or had warnings because of unintended inhibition of hERG. The channel is composed of four alpha subunits, each spanning the membrane six times (S1–S6 regions), with specialized structures dedicated to voltage sensing and ion selectivity. Beyond the heart, hERG is also expressed in the nervous system and various cancer cell lines, where its roles are less defined but may relate to cellular excitability and proliferation. Because inadvertent blockade by pharmaceuticals poses a serious pro-arrhythmic risk, **hERG is both a key therapeutic target and an important antitarget in drug safety pharmacology**[1][3][4][5][6].

Other names

Human ether-à-go-go-related gene product alpha subunitKCNH2 (gene symbol)Kv11.1Ether-à-go-go-related gene potassium channelhERG1

Drug block: Many drugs bind within the central cavity or hydrophobic pocket of the hERG channel, physically occluding potassium flow and prolonging repolarization of the cardiac action potential. QT interval prolongation: Blockade leads to prolongation of action potential duration, resulting in QT interval prolongation on ECG.