TheG protein-coupled inwardly rectifying potassium channels (GIRKs) are a family oflipid-gatedinward-rectifier potassium ion channels which are activated (opened) by the signaling lipid PIP2 and asignal transduction cascade starting withligand-stimulatedG protein-coupled receptors (GPCRs).[1][2] GPCRs in turn release activatedG-protein βγ- subunits (Gβγ) from inactiveheterotrimeric 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 inhyperpolarization of the cell membrane.[3] G protein-coupled inwardly rectifying potassium channels are a type ofG protein-gated ion channels because of this direct interaction of G protein subunits with GIRK channels. The activation likely works by increasing the affinity of the channel for PIP2. In high concentration PIP2 activates the channel absent G-protein, but G-protein does not activate the channel absent PIP2.
GIRK1 to GIRK3 are distributed broadly in the central nervous system, where their distributions overlap.[4][5][6] GIRK4, instead, is found primarily in the heart.[7]
Examples of GIRKs include a subset of potassium channels in the heart, which, when activated byparasympathetic signals such asacetylcholine throughM2 muscarinic receptors, causes an outward current of potassium, which slows down theheart rate.[9][10] These are calledmuscarinic potassium channels (IKACh) and are heterotetramers composed of twoGIRK1 and twoGIRK4 subunits.[7][11]
^Chen SC, Ehrhard P, Goldowitz D, Smeyne RJ (December 1997). "Developmental expression of the GIRK family of inward rectifying potassium channels: implications for abnormalities in the weaver mutant mouse".Brain Res.778 (2):251–64.doi:10.1016/S0006-8993(97)00896-2.PMID9459542.S2CID13599513.
^abKrapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE (1995). "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K+-channel proteins".Nature.374 (6518):135–41.Bibcode:1995Natur.374..135K.doi:10.1038/374135a0.PMID7877685.S2CID4334467.
^Svízenská I, Dubový P, Sulcová A (October 2008). "Cannabinoid Receptors 1 and 2 (CB1 and CB2), Their Distribution, Ligands and Functional Involvement in Nervous System Structures — A Short Review".Pharmacology Biochemistry and Behavior.90 (4):501–11.doi:10.1016/j.pbb.2008.05.010.PMID18584858.S2CID4851569.
