Kir4.1
Description: potassium inwardly-rectifying channel, subfamily J, member 10 Gene: Kcnj10 Alias: Kir4.1, kcnj10, BIR10, BIRK-1
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
Gene
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_002241.5 | 5205 | |
Mouse | NM_001039484.1 | 5407 | |
Rat | NM_031602.2 | 1438 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Structure
Kir4.1 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
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]).
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]).
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]).
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
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Jiang C
et al.
An alternative approach to the identification of respiratory central chemoreceptors in the brainstem.
,
2001
Dec
, 129 (141-57).
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).
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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