Inward rectifier potassium channel 2 (Kir2.1) (Kir2.1)

Inward rectifier potassium channel 2 (Kir2.1) is a strongly inward-rectifying potassium-selective ion channel encoded by the KCNJ2 gene, classified in the Kir2.x subfamily, and primarily expressed in cardiac, neuronal, and skeletal muscle tissues. Its main physiological role is to stabilize the resting membrane potential and regulate excitability in excitable cells by permitting K+ entry more efficiently than exit, a property governed by channel blockade via intracellular polyamines and Mg2+. Kir2.1 is critically involved in cardiac action potential repolarization, muscle contraction, and development of heart and bone. Pathogenic variants cause Andersen-Tawil syndrome (characterized by arrhythmias, periodic paralysis, and dysmorphic features) and have been implicated in other cardiac arrhythmias such as short QT syndrome. Several known pharmaceuticals, including flecainide, propafenone, and timolol, act as modulators via both primary and off-target mechanisms, providing leads for drug development but also potential safety liabilities. Defects in its structure or regulation profoundly affect membrane electrical properties and thus can have lethal consequences in cardiac or muscle systems.

Other names

Cardiac inward rectifier potassium channelhIRK1IRK-1IRK1Inward rectifier K(+) channel Kir2.1Potassium channel, inwardly rectifying subfamily J member 2KCNJ2 (gene name)

Direct activation by binding to Cys311 (flecainide, propafenone, timolol)—potential to design isoform-specific activators for Kir2.1. Drugs primarily designed for other cardiac targets may have off-target effects on Kir2.1