Kir4.1

Description: potassium inwardly-rectifying channel, subfamily J, member 10
Gene: Kcnj10
Alias: Kir4.1, kcnj10, BIR10, BIRK-1

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Introduction

The Kir channel family comprises more than 15 members that fall into seven subfamilies (Kir1.x through Kir7.x) (Kubo et al., 2005 [1008]).

KCNJ10 (also known as KIR1.2; KIR4.1; SESAME; BIRK-10; KCNJ13-PEN) encodes Kir4.1, potassium inwardly-rectifying channel, subfamily J, member 10, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes.

http://www.ncbi.nlm.nih.gov/gene/3766

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Gene

Species	NCBI gene ID	Chromosome	Position
Human	3766	1	32693
Mouse	16513	1	32875
Rat	29718	13	33357

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_002241.5	5205
Mouse	NM_001039484.1	5407
Rat	NM_031602.2	1438

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	P78508	379
Mouse	Q9JM63	379
Rat	P49655	379

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_031602.2

1438

NP_113790.2

379

Predicted

XM_017598774.2

5344

XP_017454263.1

379

transcript variant X1

isoform X1

XM_017598775.2

5059

XP_017454264.1

381

transcript variant X4

isoform X2

XM_039090649.1

5059

XP_038946577.1

379

transcript variant X3

isoform X1

XM_039090648.1

5060

XP_038946576.1

379

transcript variant X2

isoform X1

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Post-Translational Modifications

PTM

Position

Type

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Structure

Kir4.1 predicted AlphaFold size

Species	Area (Å²)	Reference
Human	3505.22	source
Mouse	3569.08	source
Rat	4480.27	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Expression and Distribution

It was shown that, among them, Kir4.1 and Kir5.1 are expressed predominantly in brain astrocytes and retinal Muller cells (Takumi et al., 1995 [1009]; Ishii et al., 1997 [1010], 2003; Poopalasundaram et al., 2000 [1011]; Hibino et al., 2004 [1012]).

The Kir4.1 and Kir5.1 subunits are expressed in the proximal convoluted tubule, the distal convoluted tubule and the cortical collecting duct of the kidney (Tucker [1019], Tanemoto [1013], Tanemoto [1027]).

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CNS Sub-cellular Distribution

Kir4.1 alone exists at the end-feet of retinal Mueller cells, and both Kir4.1 and Kir5.1, are detected in the cell body (Ishii [1010]).

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Function

Astroglial Kir channels are either homotetramers of Kir4.1 or heterotetramers of Kir4.1 and Kir5.1, both of which constitutively allow large inward K+ currents at potentials negative to EK and small, but significant, outward K+ currents at those positive to EK (Takumi et al., 1995 [1009]; Ishii et al., 1997 [1010]; Tanemoto et al., 2000 [1013]; Higashi et al., 2001 [1014]). Thus, depending on the difference between local EK and the membrane potential of astrocytes, these Kir channels can mediate either absorption or extrusion of K+ across the astroglial cell membrane and thus can act as the spatial K+-buffering current. (Su [202])

In addition, Kir4.1 channel and the water channel, aquaporin-4, are colocalized in certain membrane domains of brain astrocytes and Muller cells, suggesting that spatial K+ buffering may couple with water movement across the astroglial membrane (Nagelhus et al., 1999 [1015]; Amiry-Moghaddam et al., 2003 [1016]; Puwarawuttipanit et al., 2006 [1017]).

Kir4.1 and Kir5.1 subunits are expressed in the kidney, eye and brainstem suggests that the channel may be a candidate molecule for the regulation of K+ homeostasis and central CO2 chemoreception (Pessia [1020], Yang [1023], Jiang [1025], Wu [1026]).

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Interaction

Tricyclic antidepressants (TCAs) influence the astroglial Kir4.1 channels expressed in HEK293T cells. Su et al. [202] demonstrated that nortriptyline and other TCAs, including amitriptyline, desipramine, and imipramine, inhibit homomeric Kir4.1 channels in a voltage- and time-dependent fashion.

Unlike other Kir family members, heteromultimerization of inter-subfamily members Kir4.1 and Kir5.1 leads to a channel with distinct functional properties (Casamassima[1018], Konstas [1019], Pessia [1020], Tanemoto [1013], Tucker [1021], Xu [1022], Yang [1023]). Of particular interest in these newly emerging properties is the enhanced sensitivity to intracellular pH (pKa 7.45), allowing the heteromeric Kir4.1–Kir5.1 channel to detect pH changes at physiological levels (Pessia [1020], Xu [1022], Yang [1023], Xui [1024]).

References

202

Su S et al. Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline.
J. Pharmacol. Exp. Ther., 2007 Feb , 320 (573-80).

203

Rojas A et al. Protein kinase C dependent inhibition of the heteromeric Kir4.1-Kir5.1 channel.
Biochim. Biophys. Acta, 2007 Sep , 1768 (2030-42).

204

Specific localization of an inwardly rectifying K(+) channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its possible involvement in K(+) recycling for the H(+)-K(+)-pump.
J. Physiol. (Lond.), 2002 Apr 1 , 540 (85-92).

1008

Kubo Y et al. International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels.
Pharmacol. Rev., 2005 Dec , 57 (509-26).

1009

Takumi T et al. A novel ATP-dependent inward rectifier potassium channel expressed predominantly in glial cells.
J. Biol. Chem., 1995 Jul 7 , 270 (16339-46).

1010

Ishii M et al. Differential expression and distribution of Kir5.1 and Kir4.1 inwardly rectifying K+ channels in retina.
Am. J. Physiol., Cell Physiol., 2003 Aug , 285 (C260-7).

1011

Poopalasundaram S et al. Glial heterogeneity in expression of the inwardly rectifying K(+) channel, Kir4.1, in adult rat CNS.
Glia, 2000 Jun , 30 (362-72).

1012

Hibino H et al. Differential assembly of inwardly rectifying K+ channel subunits, Kir4.1 and Kir5.1, in brain astrocytes.
J. Biol. Chem., 2004 Oct 15 , 279 (44065-73).

1013

Tanemoto M et al. In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1.
J. Physiol. (Lond.), 2000 Jun 15 , 525 Pt 3 (587-92).

1014

Higashi K et al. An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain.
Am. J. Physiol., Cell Physiol., 2001 Sep , 281 (C922-31).

1015

Nagelhus EA et al. Immunogold evidence suggests that coupling of K+ siphoning and water transport in rat retinal Müller cells is mediated by a coenrichment of Kir4.1 and AQP4 in specific membrane domains.
Glia, 1999 Mar , 26 (47-54).

1016

Amiry-Moghaddam M et al. An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.
Proc. Natl. Acad. Sci. U.S.A., 2003 Feb 18 , 100 (2106-11).

1017

Puwarawuttipanit W et al. Differential effect of alpha-syntrophin knockout on aquaporin-4 and Kir4.1 expression in retinal macroglial cells in mice.
Neuroscience, 2006 , 137 (165-75).

1018

Casamassima M et al. Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels.
J. Biol. Chem., 2003 Oct 31 , 278 (43533-40).

1019

Konstas AA et al. Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels.
Am. J. Physiol., Cell Physiol., 2003 Apr , 284 (C910-7).

1020

Pessia M et al. Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1.
J. Physiol. (Lond.), 2001 Apr 15 , 532 (359-67).

1021

Tucker SJ et al. pH dependence of the inwardly rectifying potassium channel, Kir5.1, and localization in renal tubular epithelia.
J. Biol. Chem., 2000 Jun 2 , 275 (16404-7).

1022

Xu H et al. Modulation of kir4.1 and kir5.1 by hypercapnia and intracellular acidosis.
J. Physiol. (Lond.), 2000 May 1 , 524 Pt 3 (725-35).

1023

Yang Z et al. Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.
J. Gen. Physiol., 2000 Jul 1 , 116 (33-45).

1024

Cui N et al. Modulation of the heteromeric Kir4.1-Kir5.1 channels by P(CO(2)) at physiological levels.
J. Cell. Physiol., 2001 Nov , 189 (229-36).

1025

Jiang C et al. An alternative approach to the identification of respiratory central chemoreceptors in the brainstem.
, 2001 Dec , 129 (141-57).

1026

Wu J et al. Expression and coexpression of CO2-sensitive Kir channels in brainstem neurons of rats.
J. Membr. Biol., 2004 Feb 1 , 197 (179-91).

1027

Tanemoto M et al. PDZ binding motif-dependent localization of K+ channel on the basolateral side in distal tubules.
Am. J. Physiol. Renal Physiol., 2004 Dec , 287 (F1148-53).

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To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/50/ , accessed on 2024 Dec 21

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