Potassium inward rectifier channel subfamily J member 3 (KCNJ3)

Potassium inward rectifier channel subfamily J member 3 (KCNJ3), commonly referred to as GIRK1, is a transmembrane protein that serves as a core subunit of G protein-activated inward rectifier potassium (GIRK) channels. These channels are predominantly localized in the central nervous system and the cardiac atria, where they play a fundamental role in controlling membrane excitability [UniProt: P48549]. Upon the activation of G protein-coupled receptors (GPCRs), such as the muscarinic M2 or adenosine A1 receptors, liberated Gβγ subunits bind directly to the GIRK complex, causing the channel to open and allowing potassium ions to flow out of the cell [PubMed: 10457636]. This efflux results in membrane hyperpolarization, which in the heart slows the heart rate (the IKACh current) and in the brain modulates neuronal firing rates [PubMed: 25484347]. Pathologically, KCNJ3 has been implicated in the development of atrial fibrillation and certain forms of epilepsy, and it has recently emerged as a potential biomarker and driver for metastasis in breast cancer [PubMed: 29532585]. Pharmacological efforts are currently focused on developing subunit-selective inhibitors, like NTC-801, to treat supraventricular arrhythmias while minimizing off-target effects in other tissues [PubMed: 30045831].

Other names

GIRK1KIR3.1KGAInward rectifier K(+) channel Kir3.1BIR1

Modulation of potassium efflux through G protein-activated inward rectifier complexes to regulate cellular membrane potential and excitability.