Inward rectifier potassium channel 2.1 (Kir2.1)

Inward rectifier potassium channel 2.1 (Kir2.1, encoded by the KCNJ2 gene) is a tetrameric membrane protein channel that mediates strong inward rectification of potassium ions, favoring K⁺ influx over efflux to maintain the cell's resting membrane potential[1][4][7][9]. Highly expressed in the heart, skeletal muscle, and central nervous system, Kir2.1 is crucial for stabilizing electrical excitability, facilitating action potential repolarization, and ensuring proper rhythmicity in cardiac myocytes[2][7][9]. Dysfunctional Kir2.1 channels are associated with severe clinical disorders, including Andersen-Tawil syndrome (featuring periodic paralysis, cardiac arrhythmias, and developmental malformations) and short QT syndrome, with both hypo- and hyperactivity posing life-threatening risks[9]. In macrophages, Kir2.1 modulates immunometabolic states and inflammatory responses by controlling nutrient transporter surface expression and nutrient uptake[3]. Kir2.1 is directly and selectively inhibited by small molecules such as ML133, and is blocked (with varying sensitivity) by antiarrhythmic drugs like quinidine and propafenone[2][5]. Channel activity is regulated by phosphoinositide binding (particularly PIP₂), with structural transitions between compact and extended states mediated by ligand interactions at the cytoplasmic terminal domains[1][7].

Other names

KCNJ2Kir2.1 channelInwardly rectifying potassium channel Kir2.1

Channel blockade (direct pore blockage by small molecules such as quinidine, ML133) Voltage-dependent block (by endogenous polyamines and Mg²⁺) Modulation by phosphoinositides (notably PIP₂)