Cardiac delayed rectifier potassium channel (IK) (IK)

The cardiac delayed rectifier potassium channel is a group of voltage-gated ion channels essential for the repolarization phase of the cardiac action potential (StatPearls: Physiology, Cardiac Potassium Channels). It is functionally divided into three components based on their activation kinetics: the rapid (IKr), slow (IKs), and ultra-rapid (IKur) currents. These currents are mediated by specific alpha-subunits, primarily KCNH2 (hERG) for IKr, KCNQ1 for IKs, and KCNA5 for IKur, often in association with regulatory beta-subunits like KCNE1 (PubMed: PMC2821710). By allowing the efflux of potassium ions from myocytes, these channels facilitate the return of the membrane potential to its resting state, thereby determining the duration of the action potential and the refractory period of the heart (UniProt: KCNH2, KCNQ1). Dysfunction of these channels, whether due to genetic mutations or pharmacological interference, is a major cause of cardiac arrhythmias. Mutations in KCNH2 or KCNQ1 are the most common causes of congenital Long QT Syndrome, which predisposes individuals to syncope and sudden cardiac death. In clinical pharmacology, many drugs can inadvertently block the IKr component, leading to drug-induced QT prolongation and the life-threatening arrhythmia Torsades de Pointes (FDA: hERG safety guidelines). Consequently, screening for IKr (hERG) inhibition is a mandatory safety step in modern drug development. Conversely, selective blockers of IKur are being investigated as potential treatments for atrial fibrillation due to their localized expression in the atria.

Other names

Cardiac delayed rectifier potassium currentDelayed rectifier K+ currentIKIKrIKsIKurhERG channelKCNQ1/KCNE1 channelKv1.5 channel

Blockade of potassium efflux to prolong the cardiac action potential duration and effective refractory period.