Description: potassium inwardly-rectifying channel, subfamily J, member 9
Gene: Kcnj9     Synonyms: Kir3.3, Girk3, Kcnj9

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KCNJ9 (also known as GIRK3; KIR3.3) encodes the integral membrane protein Kir3.3. This is a potassium inwardly-rectifying channel, subfamily J, member 9, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins. It associates with another G-protein-activated potassium channel to form a heteromultimeric pore-forming complex.

G protein-gated inwardly rectifying potassium (GIRK or Kir3) channel activity is important for regulating excitability in the heart and brain (Stanfield et al. 2002 [957]).



RGD ID Chromosome Position Species
621440 13 88311500-88318875 Rat
734275 1 174251164-174259394 Mouse
1343442 1 160051360-160059212 Human

Kcnj9 : potassium inwardly-rectifying channel, subfamily J, member 9



Acc No Sequence Length Source
NM_053834 n/A n/A NCBI
NM_008429 n/A n/A NCBI
NM_004983 n/A n/A NCBI



Accession Name Definition Evidence
GO:0016021 integral to membrane Penetrating at least one phospholipid bilayer of a membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. When used to describe a protein, indicates that all or part of the peptide sequence is embedded in the membrane. IEA
GO:0016020 membrane Double layer of lipid molecules that encloses all cells, and, in eukaryotes, many organelles; may be a single or double lipid bilayer; also includes associated proteins. IEA

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Recombinantly expressed NCAM180 specifically reduces inward currents of neuron-specific Kir3.1/ 3.2 and Kir3.1/3.3 but not Kir3.1/3.4 channels in Xenopus oocytes and CHO cells (Delling [990]).

NCAM, TrkB and Kir3.3 interact directly with each other via their intracellular domains. Overexpression of the developmentally late appearing Kir3.3 subunit leads to a decrease in NCAM-mediated neurite outgrowth. Kir3.3 chan- nel expression at the cell surface; thus activity is regulated by NCAM and TrkB independently of BDNF ligand binding. These observations indicate that the interplay of recognition molecules, neurotrophin receptors, and ion channels regulate neurite outgrowth. Kleene [988]


Kir3 channels are activated following stimulation of G protein-coupled receptors (GPCRs) that use the Gi/o family of G proteins. Stimulation of the GPCR promotes exchange of GDP for GTP on the Gα subunit which, in turn, leads to activation of the Gα subunit and the Gβγ dimer. Gβγ dimers bind to and activate Kir3 channels (Reuveny et al. 1994 [968]; Wickman et al. 1994 [969]; Huang et al. 1995 [970]). Gα subunits are required for terminating Kir3 activation. The intrinsic GTPase activity of the Gα subunit hydrolyses GTP, leading to inactivation of the Gβγ dimer. Regulator of G protein signalling (RGS) proteins accelerate the GTPase activity of Gα subunits (GAP), leading to faster activation and deactivation of Kir3 channels (Doupnik et al. 1997 [971]). (From Fowler [965])







Kir3.3 subunit protein is expressed in raphe-derived axons at the light and electron microscopic level, but none of the other Kir3 subfamily members or the KATP channel subunits Kir6.1 and Kir6.2. (Pruess [993])

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Kir3.3 is expressed in mouse brain. Kofuji [195]

5-HT autoreceptors and G protein-gated inwardly rectifying potassium channels (Kir3/GIRK family), as well as their functional connectivity, has been demonstrated in raphe neurons (Penington [994]).

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The GluR7 receptor gene GRIK3 is located on chromosome 1p34–33, where a significant linkage with schizo- phrenia has been reported (DeLisi et al., 2002 [991]. Significant changes of GluR7 expression in schizophrenia have been reported in multiple brain regions (Sokolov, 1998 [992]). (From [989])

The serotonergic system of the brainstem raphe is involved in mood control, the sleep-wake cycle, auto- nomic function, and stress response. The axons of certain dorsal raphe neurons form a dense serotonergic supraependymal plexus lining the brain ventricles, likely regulating ependymal metabolism and activity including ciliary movements and glucose homeostasis. In raphe neurons, serotonin exerts its function partly via 5-HT autoreceptors and G protein-gated inwardly rectifying potassium channels (Kir3/GIRK). Kir3.3 containing potassium channels may be of functional importance in autoregulation and excitability of supraependymal fibres and the complex serotonergic regulation along the parenchyma/CSF border. (Pruess [993])

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Single channel Conductance of Kir3.3/Kir3.1 in CHO

Kv.11.1 Kir3.1/3.3 basal activity at different voltages applied to the patch membrane. No channel activity was observed at +60 mV





Stanfield PR et al. Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
Rev. Physiol. Biochem. Pharmacol., 2002 , 145 (47-179).


Doupnik CA et al. RGS proteins reconstitute the rapid gating kinetics of gbetagamma-activated inwardly rectifying K+ channels.
Proc. Natl. Acad. Sci. U.S.A., 1997 Sep 16 , 94 (10461-6).


DeLisi LE et al. Genome-wide scan for linkage to schizophrenia in a Spanish-origin cohort from Costa Rica.
Am. J. Med. Genet., 2002 Jul 8 , 114 (497-508).


Prüss H et al. Expression of Kir3.3 potassium channel subunits in supraependymal axons.
Neurosci. Lett., 2008 Nov 7 , 445 (89-93).



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