G-protein-coupled inwardly-rectifying potassium channel (GIRK) (GIRK)

G-protein-coupled inwardly-rectifying potassium (GIRK) channels are a family of potassium channels (Kir3.1 to Kir3.4) that play a fundamental role in controlling cellular excitability. These channels are uniquely activated by the direct binding of G-protein beta-gamma (Gβγ) subunits following the stimulation of Gi/o-coupled G protein-coupled receptors (GPCRs) such as muscarinic M2, GABA-B, and opioid receptors (Lüscher & Slesinger, 2010, Nature Reviews Neuroscience). In the heart, GIRK channels (specifically GIRK1/GIRK4 heteromers) mediate the vagal slowing of the heart rate, while in the brain, they contribute to inhibitory postsynaptic potentials and regulate neuronal firing (Hibino et al., 2010, Physiological Reviews). Dysfunction or mutations in GIRK channels are implicated in various pathologies, including atrial fibrillation, epilepsy, and primary aldosteronism (Whorton & MacKinnon, 2013, Cell). Because of their widespread involvement in neurotransmission and cardiac rhythm, they are considered promising therapeutic targets for treating arrhythmias and neuropsychiatric conditions (Nimitvilai et al., 2018, Journal of Neuroscience Research).

Other names

Kir3 channelInwardly rectifying potassium channel subfamily JMuscarinic-gated potassium channelKCNJ3KCNJ5KCNJ6KCNJ9

Activation by G-protein beta-gamma (Gβγ) subunits released from Gi/o-coupled G protein-coupled receptors (GPCRs), resulting in potassium efflux and membrane hyperpolarization.