G protein-coupled inwardly-rectifying potassium channel: Difference between revisions

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{{infobox protein
 
{{protein
| Name = [[KCNJ3|potassium inwardly-rectifying channel, subfamily J, member 3]]
| Name = [[KCNJ3|potassium inwardly-rectifying channel, subfamily J, member 3]]
| caption =  
| caption =  
Line 7: Line 5:
| width =  
| width =  
| HGNCid = 6264
| HGNCid = 6264
| Symbol = [[KCNJ3]]
| Symbol = KCNJ3
| AltSymbols = Kir3.1, GIRK1, KGA
| AltSymbols = Kir3.1, GIRK1, KGA
| IUPHAR_id = yes
| EntrezGene = 3760
| EntrezGene = 3760
| OMIM = 601534
| OMIM = 601534
Line 20: Line 19:
| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = [[KCNJ6|potassium inwardly-rectifying channel, subfamily J, member 6]]
| Name = [[KCNJ6|potassium inwardly-rectifying channel, subfamily J, member 6]]
| caption =  
| caption =  
Line 26: Line 25:
| width =  
| width =  
| HGNCid = 6267
| HGNCid = 6267
| Symbol = [[KCNJ6]]
| Symbol = KCNJ6
| AltSymbols = KCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
| AltSymbols = KCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
| IUPHAR_id = yes
| EntrezGene = 3763
| EntrezGene = 3763
| OMIM = 600877
| OMIM = 600877
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = [[KCNJ9|potassium inwardly-rectifying channel, subfamily J, member 9]]
| Name = [[KCNJ9|potassium inwardly-rectifying channel, subfamily J, member 9]]
| caption =  
| caption =  
Line 45: Line 45:
| width =  
| width =  
| HGNCid = 6270
| HGNCid = 6270
| Symbol = [[KCNJ9]]
| Symbol = KCNJ9
| AltSymbols = Kir3.3, GIRK3
| AltSymbols = Kir3.3, GIRK3
| IUPHAR_id = yes
| EntrezGene = 3765
| EntrezGene = 3765
| OMIM = 600932
| OMIM = 600932
Line 58: Line 59:
| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = [[KCNJ5|potassium inwardly-rectifying channel, subfamily J, member 5]]
| Name = [[KCNJ5|potassium inwardly-rectifying channel, subfamily J, member 5]]
| caption =  
| caption =  
Line 64: Line 65:
| width =  
| width =  
| HGNCid = 6266
| HGNCid = 6266
| Symbol = [[KCNJ5]]
| Symbol = KCNJ5
| AltSymbols = Kir3.4, CIR, KATP1, GIRK4
| AltSymbols = Kir3.4, CIR, KATP1, GIRK4
| IUPHAR_id = yes
| EntrezGene = 3762
| EntrezGene = 3762
| OMIM = 600734
| OMIM = 600734
Line 77: Line 79:
| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
The '''G protein-coupled inwardly-rectifying potassium channels''' ('''GIRKs''') are a family of [[inward-rectifier potassium ion channel]]s which are activated (opened) via a [[signal transduction]] cascade starting with [[ligand (biochemistry)|ligand]] stimulated [[G protein-coupled receptor]]s (GPCRs).<ref name="pmid9429760">{{cite journal | author = Dascal N | title = Signalling via the G protein-activated K<sup>+</sup> channels | journal = Cell. Signal. | volume = 9 | issue = 8 | pages = 551–73 | year = 1997 | pmid = 9429760 | issn = | doi = 10.1016/S0898-6568(97)00095-8 }}</ref><ref name="pmid9860808">{{cite journal | author = Yamada M, Inanobe A, Kurachi Y | title = G protein regulation of potassium ion channels | journal = Pharmacol. Rev. | volume = 50 | issue = 4 | pages = 723–60 | year = 1998 | pmid = 9860808 | doi = | issn = | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/50/4/723 }}</ref>  GPCRs in turn release activated [[G protein|G-protein]] βγ subunits ([[G_beta_gamma_subunits#Beta-gamma_complex|G<sub>βγ</sub>]]) from inactive [[heterotrimeric G protein]] complexes (G<sub>αβγ</sub>).  Finally the G<sub>βγ</sub> dimeric protein interacts with GIRK channels to open them so that they become permeable to potassium ions resulting in depolarization of the cell.
 
The '''G protein-coupled inwardly-rectifying potassium channels''' ('''GIRKs''') are a family of [[inward-rectifier potassium ion channel]]s which are activated (opened) via a [[signal transduction]] cascade starting with [[ligand (biochemistry)|ligand]]-stimulated [[G protein-coupled receptor]]s (GPCRs).<ref name="pmid9429760">{{cite journal | author = Dascal N | title = Signalling via the G protein-activated K<sup>+</sup> channels | journal = Cell. Signal. | volume = 9 | issue = 8 | pages = 551–73 | year = 1997 | pmid = 9429760| doi = 10.1016/S0898-6568(97)00095-8 }}</ref><ref name="pmid9860808">{{cite journal |vauthors=Yamada M, Inanobe A, Kurachi Y | title = G protein regulation of potassium ion channels | journal = Pharmacological Reviews | volume = 50 | issue = 4 | pages = 723–60 |date=December 1998 | pmid = 9860808 | doi = | url = http://pharmrev.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9860808}}</ref>  GPCRs in turn release activated [[G protein|G-protein]] βγ- subunits ([[G beta gamma subunits#Beta-gamma complex|G<sub>βγ</sub>]]) from inactive [[heterotrimeric G protein]] complexes (G<sub>αβγ</sub>).  Finally, the G<sub>βγ</sub> dimeric protein interacts with GIRK channels to open them so that they become permeable to potassium ions, resulting in [[Hyperpolarization (biology)|hyperpolarization]] of the cell membrane.<ref name="GIRK" /> G protein-coupled inwardly-rectifying potassium channels are a type of [[G protein-gated ion channel]]s 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.<ref name="pmid7702616">{{cite journal |vauthors=Kobayashi T, Ikeda K, Ichikawa T, Abe S, Togashi S, Kumanishi T | title = 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 | journal = Biochem. Biophys. Res. Commun. | volume = 208 | issue = 3 | pages = 1166–73 |date=March 1995 | pmid = 7702616 | doi = 10.1006/bbrc.1995.1456| url =  }}</ref><ref name="pmid8642402">{{cite journal |vauthors=Karschin C, Dissmann E, Stühmer W, Karschin A | title = IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain | journal = J. Neurosci. | volume = 16 | issue = 11 | pages = 3559–70 |date=June 1996 | pmid = 8642402 | doi = | url =  }}</ref><ref name="pmid9459542">{{cite journal |vauthors=Chen SC, Ehrhard P, Goldowitz D, Smeyne RJ | title = Developmental expression of the GIRK family of inward rectifying potassium channels: implications for abnormalities in the weaver mutant mouse | journal = Brain Res. | volume = 778 | issue = 2 | pages = 251–64 |date=December 1997 | pmid = 9459542 | doi = 10.1016/S0006-8993(97)00896-2| url =  }}</ref> GIRK4, instead, is found primarily in the heart.<ref name="pmid7877685" />


==Subtypes==
==Subtypes==
Line 105: Line 110:


==Examples==
==Examples==
A wide variety of G-protein coupled receptors activate GIRKs including the [[muscarinic acetylcholine receptor M2|M<sub>2</sub>-muscarinic]], [[adenosine A1 receptor|A<sub>1</sub>-adenosine]], [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic]], [[dopamine receptor D2|D<sub>2</sub>-dopamine]], [[mu Opioid receptor|μ-]] [[delta Opioid receptor|δ-]], and [[kappa Opioid receptor|κ-]][[opioid receptor|opioid]], [[5-HT1A receptor|5-HT<sub>1A</sub> serotonin]], [[somatostatin receptor|somatostatin]], [[galanin receptor|galanin]], [[metabotropic glutamate receptor|m-Glu]], [[GABAB receptor|GABA<sub>B</sub>]], and [[lysophospholipid receptor|sphingosine-1-phosphate]] receptors.<ref name="pmid9860808"/>
A wide variety of G protein-coupled receptors activate GIRKs, including the [[muscarinic acetylcholine receptor M2|M<sub>2</sub>-muscarinic]], [[adenosine A1 receptor|A<sub>1</sub>-adenosine]], [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic]], [[dopamine receptor D2|D<sub>2</sub>-dopamine]], [[mu Opioid receptor|μ-]] [[delta Opioid receptor|δ-]], and [[kappa Opioid receptor|κ-]][[opioid receptor|opioid]], [[5-HT1A receptor|5-HT<sub>1A</sub> serotonin]], [[somatostatin receptor|somatostatin]], [[galanin receptor|galanin]], [[metabotropic glutamate receptor|m-Glu]], [[GABAB receptor|GABA<sub>B</sub>]], [[TAAR1]], and [[lysophospholipid receptor|sphingosine-1-phosphate]] receptors.<ref name="pmid9860808"/><ref name="GIRK">{{cite journal |vauthors=Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G, Mercuri NB | title = Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons | journal = Front Syst Neurosci | volume = 5 | issue = | pages = 56 | year = 2011 | pmid = 21772817 | pmc = 3131148 | doi = 10.3389/fnsys.2011.00056 | quote = 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. }}</ref>


Examples of GIRKs include a subset of potassium channels in the heart which when activated by [[parasympathetic]] signals such as [[acetylcholine]] through [[M2 receptors|M2 muscarinic receptors]], causes an outward current of potassium which slows down the [[heart rate]].<ref name="pmid8521474">{{cite journal | author = Kunkel MT, Peralta EG | title = Identification of domains conferring G protein regulation on inward rectifier potassium channels | journal = Cell | volume = 83 | issue = 3 | pages = 443–9 | year = 1995 | pmid = 8521474 | doi = 10.1016/0092-8674(95)90122-1 | issn = }}</ref><ref name="pmid10414308">{{cite journal | author = Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE | title = Structure, G protein activation, and functional relevance of the cardiac G protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = Ann. N. Y. Acad. Sci. | volume = 868 | issue = | pages = 386–98 | year = 1999 | pmid = 10414308 | doi = | issn = | url = http://www.annalsnyas.org/cgi/content/abstract/868/1/386 }}</ref>  These are called ''muscarinic potassium channels'' (I<sub>KACh</sub>) and are heterotetramers comprised of two [[KCNJ3|GIRK1]] and two [[KCNJ5|GIRK4]] subunits.<ref name="pmid7877685">{{cite journal | author = Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE | title = The G-protein-gated atrial K<sup>+</sup> channel I<sub>KACh</sub> is a heteromultimer of two inwardly rectifying K<sup>+</sup>-channel proteins | journal = Nature | volume = 374 | issue = 6518 | pages = 135–41 | year = 1995 | pmid = 7877685 | doi = 10.1038/374135a0 | issn = }}</ref><ref name="pmid9478984">{{cite journal | author = Corey S, Krapivinsky G, Krapivinsky L, Clapham DE | title = Number and stoichiometry of subunits in the native atrial G-protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = J. Biol. Chem. | volume = 273 | issue = 9 | pages = 5271–8 | year = 1998 | pmid = 9478984 | doi = 10.1074/jbc.273.9.5271 | issn = }}</ref>
Examples of GIRKs include a subset of potassium channels in the heart, which, when activated by [[parasympathetic]] signals such as [[acetylcholine]] through [[M2 receptors|M2 muscarinic receptors]], causes an outward current of potassium, which slows down the [[heart rate]].<ref name="pmid8521474">{{cite journal |vauthors=Kunkel MT, Peralta EG | title = Identification of domains conferring G protein regulation on inward rectifier potassium channels | journal = Cell | volume = 83 | issue = 3 | pages = 443–9 | year = 1995 | pmid = 8521474 | doi = 10.1016/0092-8674(95)90122-1 }}</ref><ref name="pmid10414308">{{cite journal |vauthors=Wickman K, Krapivinsky G, Corey S, Kennedy M, Nemec J, Medina I, Clapham DE | title = Structure, G protein activation, and functional relevance of the cardiac G protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = Ann. N. Y. Acad. Sci. | volume = 868 | issue = 1| pages = 386–98 | year = 1999 | pmid = 10414308 | doi = 10.1111/j.1749-6632.1999.tb11300.x| url = http://www.annalsnyas.org/cgi/content/abstract/868/1/386 }}</ref>  These are called ''muscarinic potassium channels'' (I<sub>KACh</sub>) and are heterotetramers composed of two [[KCNJ3|GIRK1]] and two [[KCNJ5|GIRK4]] subunits.<ref name="pmid7877685">{{cite journal |vauthors=Krapivinsky G, Gordon EA, Wickman K, Velimirović B, Krapivinsky L, Clapham DE | title = The G-protein-gated atrial K<sup>+</sup> channel I<sub>KACh</sub> is a heteromultimer of two inwardly rectifying K<sup>+</sup>-channel proteins | journal = Nature | volume = 374 | issue = 6518 | pages = 135–41 | year = 1995 | pmid = 7877685 | doi = 10.1038/374135a0 }}</ref><ref name="pmid9478984">{{cite journal |vauthors=Corey S, Krapivinsky G, Krapivinsky L, Clapham DE | title = Number and stoichiometry of subunits in the native atrial G-protein-gated K<sup>+</sup> channel, I<sub>KACh</sub> | journal = J. Biol. Chem. | volume = 273 | issue = 9 | pages = 5271–8 | year = 1998 | pmid = 9478984 | doi = 10.1074/jbc.273.9.5271 }}</ref>


==References==
==References==
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* {{MeshName|G+Protein-Coupled+Inwardly-Rectifying+Potassium+Channels}}
* {{MeshName|G+Protein-Coupled+Inwardly-Rectifying+Potassium+Channels}}


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Revision as of 00:42, 26 January 2017

potassium inwardly-rectifying channel, subfamily J, member 3
Identifiers
SymbolKCNJ3
Alt. symbolsKir3.1, GIRK1, KGA
IUPHAR434
Entrez3760
HUGO6264
OMIM601534
RefSeqNM_002239
UniProtP48549
Other data
LocusChr. 2 q24.1
potassium inwardly-rectifying channel, subfamily J, member 6
Identifiers
SymbolKCNJ6
Alt. symbolsKCNJ7, Kir3.2, GIRK2, KATP2, BIR1, hiGIRK2
IUPHAR435
Entrez3763
HUGO6267
OMIM600877
RefSeqNM_002240
UniProtP48051
Other data
LocusChr. 21 q22.1
potassium inwardly-rectifying channel, subfamily J, member 9
Identifiers
SymbolKCNJ9
Alt. symbolsKir3.3, GIRK3
IUPHAR436
Entrez3765
HUGO6270
OMIM600932
RefSeqNM_004983
UniProtQ92806
Other data
LocusChr. 1 q23.2
potassium inwardly-rectifying channel, subfamily J, member 5
Identifiers
SymbolKCNJ5
Alt. symbolsKir3.4, CIR, KATP1, GIRK4
IUPHAR437
Entrez3762
HUGO6266
OMIM600734
RefSeqNM_000890
UniProtP48544
Other data
LocusChr. 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 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 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, 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 (IKACh) and are heterotetramers composed of two GIRK1 and two GIRK4 subunits.[7][10]

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. ↑ 2.0 2.1 Yamada M, Inanobe A, Kurachi Y (December 1998). "G protein regulation of potassium ion channels". Pharmacological Reviews. 50 (4): 723–60. PMID 9860808.
  3. ↑ 3.0 3.1 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. 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.
  7. ↑ 7.0 7.1 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. doi:10.1038/374135a0. PMID 7877685.
  8. ↑ 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.
  9. ↑ 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. doi:10.1111/j.1749-6632.1999.tb11300.x. PMID 10414308.
  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. doi:10.1074/jbc.273.9.5271. PMID 9478984.

External links

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