Kv1.5 and IKr

Kv1.5 (Potassium voltage-gated channel subfamily A member 5) is a voltage-gated potassium channel encoded by the KCNA5 gene, primarily responsible for the ultra-rapid delayed rectifier K+ current (IKur) in atrial myocytes, but not prominent in ventricles. It regulates atrial repolarization and has emerged as a promising atrial-selective drug target for atrial fibrillation, with several small molecule and peptide inhibitors under development. IKr refers to the potassium current mediated by the hERG channel (Potassium voltage-gated channel subfamily H member 2, Kv11.1, gene KCNH2), which is critical for repolarization of the cardiac action potential in both atria and ventricles. Blockade of hERG/IKr is associated with risk of long QT syndrome and potentially fatal arrhythmias. Drugs targeting Kv1.5 aim to avoid risks associated with IKr blockade, offering atrial selectivity for safer antiarrhythmic therapy.

Other names

KCNA5IKur channelShaker-related subfamily member 5hERGKv11.1KCNH2

Inhibition (blockade) of IKur current to prolong atrial action potential duration, antiarrhythmic by atrial-selective repolarization (for Kv1.5); Inhibition (blockade) of IKr prolongs action potential duration, but blockade may risk Torsades de Pointes (TdP); some drugs block hERG unintentionally (for IKr).