G protein–activated inwardly rectifying potassium channel (GIRK)

G protein–activated inwardly rectifying potassium channels (GIRKs) are a family of potassium ion channels that regulate cellular excitability. Activated by G-protein βγ subunits upon GPCR activation, they increase potassium permeability, hyperpolarizing the cell membrane. Composed of Kir3.1-Kir3.4 subunits, forming homo- and heterotetrameric complexes. GIRKs are involved in neuronal excitability, heart rate control, and insulin secretion. Dysfunction is linked to epilepsy, Down syndrome, Parkinson’s disease, and addiction. Modulated by RGS proteins, cholesterol, and alcohol. ML297 is a potent activator, and Tertiapin-Q is an experimental blocker. Surface expression is regulated by interactions with PDZ-domain containing proteins like SNX27.

Other names

Kir3.xInwardly Rectifying Potassium Channel Subfamily J Member 3 (KCNJ3)Kir3.1Inwardly Rectifying Potassium Channel Subfamily J Member 6 (KCNJ6)Kir3.2Inwardly Rectifying Potassium Channel Subfamily J Member 9 (KCNJ9)Kir3.3Inwardly Rectifying Potassium Channel Subfamily J Member 5 (KCNJ5)Kir3.4CIRKATP1GIRK4

Activation by G protein βγ subunits, leading to increased potassium ion permeability and hyperpolarization. Blockage at positive voltages via Mg²⁺/polyamines.