G protein-activated inward rectifier potassium channel 2 (Kir3.2)

G protein-activated inward rectifier potassium channel 2 (GIRK2 or Kir3.2) is an inwardly rectifying potassium channel encoded by the KCNJ6 gene[4][6][7]. GIRK2 forms homo- or heterotetrameric complexes, often with other GIRK (Kir3.x) subunits, and is activated by Gβγ subunits released from activated G protein-coupled receptors (GPCRs)[4]. It plays a critical role in stabilizing the resting membrane potential and in mediating inhibitory synaptic transmission in neurons, as well as regulating heart rate in cardiac myocytes[4][5][6]. Dysfunction or altered trafficking and gating of Kir3.2 channels can lead to pathologies including epilepsy, movement disorders, and cardiac arrhythmias, and they are a key therapeutic target for modulating neuronal excitability in neuropsychiatric and neurologic disease[6]. Drugs can target Kir3.2 directly or indirectly via their regulation by GPCRs (such as GABAB, muscarinic, and opioid receptors), and safety concerns include the risk of excessive inhibition of neuronal or cardiac excitability[6][4].

Other names

GIRK2KCNJ6G protein-coupled inwardly rectifying potassium channel 2Inward rectifier potassium channel 6

Channel openers (enhance potassium efflux and neuronal inhibition), Channel blockers (reduce potassium efflux and increase excitability), allosteric modulation, G protein-mediated activation via GPCRs