G protein-coupled inwardly-rectifying potassium channel

G protein-coupled inwardly-rectifying potassium channel

potassium inwardly-rectifying channel, subfamily J, member 3
Symbol KCNJ3
Alt. symbols Kir3.1, GIRK1, KGA
Entrez 3760
HUGO 6264
OMIM 601534
RefSeq NM_002239
UniProt P48549
Other data
Locus Chr. 2 q24.1
potassium inwardly-rectifying channel, subfamily J, member 6
Symbol KCNJ6
Alt. symbols KCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
Entrez 3763
HUGO 6267
OMIM 600877
RefSeq NM_002240
UniProt P48051
Other data
Locus Chr. 21 q22.1
potassium inwardly-rectifying channel, subfamily J, member 9
Symbol KCNJ9
Alt. symbols Kir3.3, GIRK3
Entrez 3765
HUGO 6270
OMIM 600932
RefSeq NM_004983
UniProt Q92806
Other data
Locus Chr. 1 q23.2
potassium inwardly-rectifying channel, subfamily J, member 5
Symbol KCNJ5
Alt. symbols Kir3.4, CIR, KATP1, GIRK4
Entrez 3762
HUGO 6266
OMIM 600734
RefSeq NM_000890
UniProt P48544
Other data
Locus Chr. 11 q24

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).[1][2] 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 hyperpolarization of the cell. G protein-coupled inwardly-rectifying potassium channels are a type of G protein-gated ion channels because of this direct activation of GIRK channels by G protein subunits.

GIRK1 to GIRK3 are distributed broadly in the central nervous system, where their distributions overlap.[3][4][5] GIRK4, instead, is found primarily in the heart.[6]


  • Subtypes 1
  • Examples 2
  • References 3
  • External links 4


protein gene aliases
GIRK1 KCNJ3 Kir3.1
GIRK2 KCNJ6 Kir3.2
GIRK3 KCNJ9 Kir3.3
GIRK4 KCNJ5 Kir3.4


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, TAAR1, and sphingosine-1-phosphate receptors.[2][7]

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.[8][9] These are called muscarinic potassium channels (IKACh) and are heterotetramers composed of two GIRK1 and two GIRK4 subunits.[6][10]


  1. ^ Dascal N (1997). "Signalling via the G protein-activated K+ channels". Cell. Signal. 9 (8): 551–73.  
  2. ^ a b Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews 50 (4): 723–60.  
  3. ^ Kobayashi T, Ikeda K, Ichikawa T, Abe S, Togashi S, Kumanishi T (March 1995). "Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain". Biochem. Biophys. Res. Commun. 208 (3): 1166–73.  
  4. ^ Karschin C, Dissmann E, Stühmer W, Karschin A (June 1996). "IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain". J. Neurosci. 16 (11): 3559–70.  
  5. ^ 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.  
  6. ^ a b Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE (March 1995). "The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins". Nature 374 (6518): 135–41.  
  7. ^ Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G, Mercuri NB (2011). "Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons". Front Syst Neurosci 5: 56.  
  8. ^ Kunkel MT, Peralta EG (1995). "Identification of domains conferring G protein regulation on inward rectifier potassium channels". Cell 83 (3): 443–9.  
  9. ^ Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE (1999). "KACh channel, I+"Structure, G protein activation, and functional relevance of the cardiac G protein-gated K. Ann. N. Y. Acad. Sci. 868 (1): 386–98.  
  10. ^ Corey S, Krapivinsky G, Krapivinsky L, Clapham DE (1998). "Number and stoichiometry of subunits in the native atrial G-protein-gated K+ channel, IKACh". J. Biol. Chem. 273 (9): 5271–8.  

External links

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels at the US National Library of Medicine Medical Subject Headings (MeSH)