KCNJ10 explained

ATP-sensitive inward rectifier potassium channel 10 is a protein that in humans is encoded by the KCNJ10 gene.^{[1] [2] [3] [4]}

Function

This gene encodes a member of the inward rectifier-type potassium channel family, K_ir4.1, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. K_ir4.1, 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.

EAST syndrome

Humans with mutations in the KCNJ10 gene that cause loss of function in related K⁺ channels can display Epilepsy, Ataxia, Sensorineural deafness and Tubulopathy, the EAST syndrome (Gitelman syndrome phenotype) reflecting roles for KCNJ10 gene products in the brain, inner ear and kidney.^[5] The K_ir4.1 channel is expressed in the Stria vascularis and is essential for formation of the endolymph, the fluid that surrounds the mechanosensitive stereocilia of the sensory hair cells that make hearing possible.^[6]

Rett Syndrome

Rett syndrome is a neurological disorder characterized by a mutation in the MeCP2 gene. This mutation results in less MeCP2. KCNJ10 expression is upregulated by the transcription factor MeCP2.^[7] MeCP2 deficiency leads to less Kir4.1 channels present on astrocytes in the brain. Since there are fewer channels allowing potassium into the cells, extracellular potassium levels are higher. Higher extracellular potassium leaves neurons more easily excitable which could contribute to the epilepsy observed in many Rett Syndrome patients.^[8]

Interactions

KCNJ10 has been shown to interact with Interleukin 16.^[9]

See also

• Inward-rectifier potassium ion channel

Further reading

• Horio Y, Hibino H, Inanobe A, Yamada M, Ishii M, Tada Y, Satoh E, Hata Y, Takai Y, Kurachi Y . 6 . Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90 . The Journal of Biological Chemistry . 272 . 20 . 12885–8 . May 1997 . 9148889 . 10.1074/jbc.272.20.12885 . free .
• Kurschner C, Mermelstein PG, Holden WT, Surmeier DJ . CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins . Molecular and Cellular Neurosciences . 11 . 3 . 161–72 . June 1998 . 9647694 . 10.1006/mcne.1998.0679 . 36534759 . D. James Surmeier .
• Kurschner C, Yuzaki M . Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein . The Journal of Neuroscience . 19 . 18 . 7770–80 . September 1999 . 10479680 . 6782450 . 10.1523/JNEUROSCI.19-18-07770.1999 .
• Schoots O, Wilson JM, Ethier N, Bigras E, Hebert TE, Van Tol HH . Co-expression of human Kir3 subunits can yield channels with different functional properties . Cellular Signalling . 11 . 12 . 871–83 . December 1999 . 10659995 . 10.1016/S0898-6568(99)00059-5 .
• Fujita A, Horio Y, Higashi K, Mouri T, Hata F, Takeguchi N, Kurachi Y . 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 . The Journal of Physiology . 540 . Pt 1 . 85–92 . April 2002 . 11927671 . 2290207 . 10.1113/jphysiol.2001.013439 .
• Farook VS, Hanson RL, Wolford JK, Bogardus C, Prochazka M . Molecular analysis of KCNJ10 on 1q as a candidate gene for Type 2 diabetes in Pima Indians . Diabetes . 51 . 11 . 3342–6 . November 2002 . 12401729 . 10.2337/diabetes.51.11.3342 . 44659955 .
• Konstas AA, Korbmacher C, Tucker SJ . Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels . American Journal of Physiology. Cell Physiology . 284 . 4 . C910–7 . April 2003 . 12456399 . 10.1152/ajpcell.00479.2002 . 2525019 .
• Casamassima M, D'Adamo MC, Pessia M, Tucker SJ . Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels . The Journal of Biological Chemistry . 278 . 44 . 43533–40 . October 2003 . 12923169 . 10.1074/jbc.M306596200 . free .
• Buono RJ, Lohoff FW, Sander T, Sperling MR, O'Connor MJ, Dlugos DJ, Ryan SG, Golden GT, Zhao H, Scattergood TM, Berrettini WH, Ferraro TN . 6 . Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility . Epilepsy Research . 58 . 2–3 . 175–83 . February 2004 . 15120748 . 10.1016/j.eplepsyres.2004.02.003 . 3186905 . free .
• Lenzen KP, Heils A, Lorenz S, Hempelmann A, Höfels S, Lohoff FW, Schmitz B, Sander T . 6 . Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy . Epilepsy Research . 63 . 2–3 . 113–8 . February 2005 . 15725393 . 10.1016/j.eplepsyres.2005.01.002 . 23643776 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Huang C, Sindic A, Hill CE, Hujer KM, Chan KW, Sassen M, Wu Z, Kurachi Y, Nielsen S, Romero MF, Miller RT . 6 . Interaction of the Ca2+-sensing receptor with the inwardly rectifying potassium channels Kir4.1 and Kir4.2 results in inhibition of channel function . American Journal of Physiology. Renal Physiology . 292 . 3 . F1073–81 . March 2007 . 17122384 . 10.1152/ajprenal.00269.2006 .

External links

• GeneReviews/NCBI/NIH/UW entry on Pendred Syndrome/DFNB4

Notes and References

1. Tada Y, Horio Y, Takumi T, Terayama M, Tsuji L, Copeland NG, Jenkins NA, Kurachi Y . 6 . Assignment of the glial inwardly rectifying potassium channel KAB-2/Kir4.1 (Kcnj10) gene to the distal region of mouse chromosome 1 . Genomics . 45 . 3 . 629–30 . November 1997 . 9367690 . 10.1006/geno.1997.4957 .
2. Shuck ME, Piser TM, Bock JH, Slightom JL, Lee KS, Bienkowski MJ . Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3) . The Journal of Biological Chemistry . 272 . 1 . 586–93 . January 1997 . 8995301 . 10.1074/jbc.272.1.586 . free .
3. Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA . 6 . International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels . Pharmacological Reviews . 57 . 4 . 509–26 . December 2005 . 16382105 . 10.1124/pr.57.4.11 . 11588492 .
4. Web site: Entrez Gene: KCNJ10 potassium inwardly-rectifying channel, subfamily J, member 10.
5. Bockenhauer D, Feather S, Stanescu HC, Bandulik S, Zdebik AA, Reichold M, Tobin J, Lieberer E, Sterner C, Landoure G, Arora R, Sirimanna T, Thompson D, Cross JH, van't Hoff W, Al Masri O, Tullus K, Yeung S, Anikster Y, Klootwijk E, Hubank M, Dillon MJ, Heitzmann D, Arcos-Burgos M, Knepper MA, Dobbie A, Gahl WA, Warth R, Sheridan E, Kleta R . 6 . Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations . The New England Journal of Medicine . 360 . 19 . 1960–70 . May 2009 . 19420365 . 3398803 . 10.1056/NEJMoa0810276 .
6. Nin F, Hibino H, Doi K, Suzuki T, Hisa Y, Kurachi Y . The endocochlear potential depends on two K+ diffusion potentials and an electrical barrier in the stria vascularis of the inner ear . Proceedings of the National Academy of Sciences of the United States of America . 105 . 5 . 1751–6 . February 2008 . 18218777 . 2234216 . 10.1073/pnas.0711463105 . 2008PNAS..105.1751N . free .
7. Kahanovitch U, Cuddapah VA, Pacheco NL, Holt LM, Mulkey DK, Percy AK, Olsen ML . MeCP2 Deficiency Leads to Loss of Glial Kir4.1 . eNeuro . 5 . 1 . ENEURO.0194–17.2018 . January 2018 . 29464197 . 5818552 . 10.1523/ENEURO.0194-17.2018 .
8. Cresto N, Pillet LE, Billuart P, Rouach N . Do Astrocytes Play a Role in Intellectual Disabilities? . Trends in Neurosciences . 42 . 8 . 518–527 . August 2019 . 31300246 . 10.1016/j.tins.2019.05.011 . 195834131 . free .
9. Kurschner C, Yuzaki M . Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein . The Journal of Neuroscience . 19 . 18 . 7770–80 . September 1999 . 10479680 . 6782450 . 10.1523/JNEUROSCI.19-18-07770.1999 .