G protein-coupled inwardly-rectifying potassium channel

potassium inwardly-rectifying channel, subfamily J, member 3
Identifiers
Symbol	KCNJ3
Alt. symbols	Kir3.1, GIRK1, KGA
IUPHAR	434
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
Identifiers
Symbol	KCNJ6
Alt. symbols	KCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
IUPHAR	435
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
Identifiers
Symbol	KCNJ9
Alt. symbols	Kir3.3, GIRK3
IUPHAR	436
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
Identifiers
Symbol	KCNJ5
Alt. symbols	Kir3.4, CIR, KATP1, GIRK4
IUPHAR	437
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 (G_βγ) from inactive heterotrimeric G protein complexes (G_αβγ). Finally, the G_βγ 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 activation of GIRK channels by G protein subunits.

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	K_ir3.1
GIRK2	KCNJ6	K_ir3.2
GIRK3	KCNJ9	K_ir3.3
GIRK4	KCNJ5	K_ir3.4

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-HT_1A serotonin, somatostatin, galanin, m-Glu, GABA_B, TAAR1, and sphingosine-1-phosphate receptors.^[2]^[3]

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 (I_KACh) and are heterotetramers composed of two GIRK1 and two GIRK4 subunits.^[7]^[10]

References

↑ 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.
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.
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.
↑ 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.
↑ 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. PMID 8642402.
↑ 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.
1 2 Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE (1995). "The G-protein-gated atrial K⁺ channel I_KACh is a heteromultimer of two inwardly rectifying K⁺-channel proteins". Nature. 374 (6518): 135–41. doi:10.1038/374135a0. PMID 7877685.
↑ 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.
↑ 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, I_KACh". Ann. N. Y. Acad. Sci. 868 (1): 386–98. doi:10.1111/j.1749-6632.1999.tb11300.x. PMID 10414308.
↑ Corey S, Krapivinsky G, Krapivinsky L, Clapham DE (1998). "Number and stoichiometry of subunits in the native atrial G-protein-gated K⁺ channel, I_KACh". J. Biol. Chem. 273 (9): 5271–8. doi:10.1074/jbc.273.9.5271. PMID 9478984.

External links

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

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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