Potassium inward rectifier channel subfamily J member 2 (Kir2.1) (Kir2.1)

The Potassium inward rectifier channel subfamily J member 2 (Kir2.1) is a pore-forming protein that plays a fundamental role in establishing the resting membrane potential and controlling the excitability of myocytes and neurons [UniProt: P60584]. It generates the inward rectifier potassium current (IK1), which is essential for the final phase of repolarization in the cardiac action potential and for maintaining a stable resting potential [PubMed: 21930144]. Mutations in the KCNJ2 gene are associated with Andersen-Tawil syndrome (ATS), a rare multisystem disorder involving periodic paralysis and ventricular arrhythmias, as well as Short QT syndrome type 3 [NIH: Genetic Home Reference]. Pharmacologically, Kir2.1 is sensitive to various blockers such as barium and antimalarial drugs like chloroquine, which can lead to drug-induced arrhythmias [PubMed: 24633823]. Research into Kir2.1 modulators is ongoing to address cardiac rhythm disorders and certain forms of epilepsy, though achieving selectivity remains a significant hurdle [PubMed: 30104301]. Its critical role in cardiac electrophysiology makes it a significant focus for safety pharmacology and drug development.

Other names

KCNJ2IRK1HHG1LQT7SQT3Inward rectifier K+ channel Kir2.1

Drugs targeting Kir2.1 primarily function as pore blockers that reduce potassium efflux, thereby prolonging the action potential duration, or as small molecule activators that enhance channel conductance to stabilize the resting membrane potential [PubMed: 20977320, PubMed: 24633823].