potassium inwardly rectifying channel, subfamily J, member 3
Identifiers
SymbolKCNJ3
Alt. symbolsKir3.1, GIRK1, KGA
IUPHAR434
NCBI gene3760
HGNC6264
OMIM601534
RefSeqNM_002239
UniProtP48549
Other data
LocusChr. 2 q24.1
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StructuresSwiss-model
DomainsInterPro
potassium inwardly rectifying channel, subfamily J, member 6
Identifiers
SymbolKCNJ6
Alt. symbolsKCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
IUPHAR435
NCBI gene3763
HGNC6267
OMIM600877
RefSeqNM_002240
UniProtP48051
Other data
LocusChr. 21 q22.1
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StructuresSwiss-model
DomainsInterPro
potassium inwardly rectifying channel, subfamily J, member 9
Identifiers
SymbolKCNJ9
Alt. symbolsKir3.3, GIRK3
IUPHAR436
NCBI gene3765
HGNC6270
OMIM600932
RefSeqNM_004983
UniProtQ92806
Other data
LocusChr. 1 q23.2
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StructuresSwiss-model
DomainsInterPro
potassium inwardly rectifying channel, subfamily J, member 5
Identifiers
SymbolKCNJ5
Alt. symbolsKir3.4, CIR, KATP1, GIRK4
IUPHAR437
NCBI gene3762
HGNC6266
OMIM600734
RefSeqNM_000890
UniProtP48544
Other data
LocusChr. 11 q24
Search for
StructuresSwiss-model
DomainsInterPro

The G protein-coupled inwardly rectifying potassium channels (GIRKs) are a family of lipid-gated inward-rectifier potassium ion channels which are activated (opened) by the signaling lipid PIP2 and 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 membrane.[3] G protein-coupled inwardly rectifying potassium channels are a type of G 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]

Subtypes

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

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, TAAR1, CB1 and CB2, and sphingosine-1-phosphate receptors.[2][3][8]

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.[9][10] These are called muscarinic potassium channels (IKACh) and are heterotetramers composed of two GIRK1 and two GIRK4 subunits.[7][11]

References

  1. ↑ Dascal N (1997). "Signalling via the G protein-activated K+ channels". Cell. Signal. 9 (8): 551–73. doi:10.1016/S0898-6568(97)00095-8. PMID 9429760.
  2. 1 2 Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 (4): 723–60. PMID 9860808.
  3. 1 2 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. doi:10.3389/fnsys.2011.00056. PMC 3131148. PMID 21772817. inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization.
  4. ↑ 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. doi:10.1006/bbrc.1995.1456. PMID 7702616.
  5. ↑ 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. doi:10.1523/JNEUROSCI.16-11-03559.1996. PMC 6578832. PMID 8642402.
  6. ↑ 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. PMID 9459542. S2CID 13599513.
  7. 1 2 Krapivinsky 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. PMID 7877685. S2CID 4334467.
  8. ↑ 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. PMID 18584858. S2CID 4851569.
  9. ↑ Kunkel MT, Peralta EG (1995). "Identification of domains conferring G protein regulation on inward rectifier potassium channels". Cell. 83 (3): 443–9. doi:10.1016/0092-8674(95)90122-1. PMID 8521474. S2CID 14720432.
  10. ↑ Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE (1999). "Structure, G protein activation, and functional relevance of the cardiac G protein-gated K+ channel, IKACh". Ann. N. Y. Acad. Sci. 868 (1): 386–98. Bibcode:1999NYASA.868..386W. doi:10.1111/j.1749-6632.1999.tb11300.x. PMID 10414308. S2CID 25949938. Archived from the original on 2006-01-29. Retrieved 2008-02-03.
  11. ↑ 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. doi:10.1074/jbc.273.9.5271. PMID 9478984.
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