Inward-rectifier potassium channel subfamily 2 (Kir2.x)

The inward-rectifier potassium channel subfamily 2 (Kir2.x) consists of four members (Kir2.1–Kir2.4) that are crucial for maintaining the resting membrane potential and controlling the excitability of neurons, cardiomyocytes, and skeletal muscle cells (Hibino et al., 2010, Physiological Reviews). These channels are characterized by their ability to conduct potassium ions more readily into the cell than out of it, a property known as inward rectification, which is mediated by the voltage-dependent block of the pore by intracellular polyamines and magnesium ions (UniProt P60584). In the heart, Kir2.1 is the primary conductor of the inward rectifier current (IK1), which is vital for the final phase of repolarization and the stability of the resting potential (De Boer et al., 2010, Cardiovascular Research). Dysregulation or genetic mutations in Kir2.x channels are associated with several clinical conditions, including Andersen-Tawil syndrome, Short QT syndrome, and various forms of atrial and ventricular arrhythmias (StatPearls, Andersen-Tawil Syndrome). Consequently, Kir2.x channels are significant therapeutic targets for antiarrhythmic drugs, although achieving isoform selectivity remains a major challenge in drug development (PubMed: 20634230).

Other names

Kir2IRKStrong inward rectifier potassium channelKCNJ subfamily 2IK1 channel

Blockade of the ion-conducting pore to inhibit the outward flow of potassium ions during the late phase of the action potential, thereby modulating membrane excitability.