Potassium voltage-gated channel subfamily H member 2 (KCNH2) (hERG)

The Potassium voltage-gated channel subfamily H member 2 (KCNH2), widely known as hERG, is a voltage-activated potassium channel that mediates the rapid component of the delayed rectifier potassium current (IKr) in the heart [UniProt: P51787]. This channel is essential for the terminal repolarization of the cardiac action potential, allowing the ventricles to relax and reset electrically between heartbeats [PubMed: 24951005]. Dysfunction of the hERG channel, whether due to genetic mutations or pharmacological inhibition, leads to Long QT syndrome (LQTS), a condition that significantly increases the risk of life-threatening ventricular arrhythmias such as Torsades de Pointes [StatPearls: NBK554411]. Because the hERG channel possesses a unique structural architecture that makes it susceptible to binding by a wide variety of chemically diverse drugs, it is a primary focus of safety pharmacology [FDA: ICH S7B]. While it is the intended therapeutic target for certain Class III anti-arrhythmic agents like dofetilide, unintended blockade by non-cardiac drugs is a leading cause of drug-induced cardiotoxicity and has resulted in numerous drug withdrawals from the market [PubMed: 12756207]. Consequently, evaluating a drug's affinity for the hERG channel is a critical and mandatory step in the modern drug development process to ensure patient safety.

Other names

hERGhERG1ERG1Kv11.1Rapid delayed rectifier potassium channelIKr channelEther-a-go-go-related gene potassium channel

Drugs typically act as pore blockers, binding to the large central cavity of the channel to inhibit the outward flow of potassium ions during the repolarization phase of the cardiac action potential [PubMed: 11514532].