G protein-coupled inwardly-rectifying potassium channel

The G protein-coupled inwardly-rectifying potassium channels (GIRKs) are a family of inward-rectifier potassium ion channels which are activated (opened) via a signal transduction cascade starting with ligand stimulated G protein-coupled receptors (GPCRs). GPCRs in turn release activated G-protein βγ subunits (Gβγ) from inactive heterotrimeric G protein complexes (Gαβγ). Finally the Gβγ dimeric protein interacts with GIRK channels to open them so that they become permeable to potassium ions resulting in depolarization of the cell.

Examples
A wide variety of G-protein coupled receptors activate GIRKs including the M2-muscarinic, A1-adenosine, α2-adrenergic, D2-dopamine, μ- δ-, and κ-opioid, 5-HT1A serotonin, somatostatin, galanin, m-Glu, GABAB, and sphingosine-1-phosphate receptors.

Examples of GIRKs include a subset of potassium channels in the heart which when activated by parasympathetic signals such as acetylcholine through M2 muscarinic receptors, causes an outward current of potassium which slows down the heart rate. These are called muscarinic potassium channels (IKACh) and are heterotetramers comprised of two GIRK1 and two GIRK4 subunits.