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Gene Review

KCNJ10  -  potassium channel, inwardly rectifying...

Homo sapiens

Synonyms: ATP-dependent inwardly rectifying potassium channel Kir4.1, ATP-sensitive inward rectifier potassium channel 10, BIRK-10, Inward rectifier K(+) channel Kir1.2, KCNJ13-PEN, ...
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Disease relevance of KCNJ10


High impact information on KCNJ10

  • Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels [3].
  • As similar results were obtained for the N terminus of another Kir channel subfamily member, Kir4.1, which could functionally substitute for the Kir2.1 N terminus, we propose a more general role of the identified N-terminal domains for post-Golgi trafficking of Kir channels [4].
  • Molecular analysis of KCNJ10 on 1q as a candidate gene for Type 2 diabetes in Pima Indians [5].
  • KCNJ10 consists of two exons, spans approximately 33 kb, and we identified eight single-nucleotide polymorphisms (SNPs), including one (SNP2) in the coding region leading to a Glu359Lys substitution [5].
  • The KCNJ10 gene is located within a region on chromosome 1q linked to type 2 diabetes in the Pima Indians and six other populations [5].

Biological context of KCNJ10


Anatomical context of KCNJ10

  • 1. Furthermore, we found that Kir4.1 as well as SAP97 distributed not diffusely but clustered in retinal glial cells [8].
  • Expression of the Kir1.2 polypeptide in Xenopus oocytes resulted in the synthesis of a K+-selective channel that exhibited an inwardly rectifying current-voltage relationship and was inhibited by external Ba2+ and Cs+ [7].
  • In contrast, when co-expressed with PSD-95, prominent clustering of Kir4.1 in the cell membrane occurred [8].
  • We examined the effects of PSD-95 on the distribution and function of Kir4.1 in a mammalian cell line [8].
  • With immunohistochemical analyses, Kir4.1 was found to be expressed in gastric parietal cells and localized specifically at their apical membrane [9].

Associations of KCNJ10 with chemical compounds

  • Significant inhibition of glutamate clearance in astrocytes with knock-down of Kir4.1 highlights the role of membrane hyperpolarization in this process [10].
  • The increase in the expression of intermediate filaments, the decrease of the whole-cell K(+) currents and of the Kir4.1 immunolabeling, and the increase in the Ca(2+) responsiveness of Müller cells were also observed in attached retinal areas surrounding the focal detachment [11].

Co-localisations of KCNJ10


Regulatory relationships of KCNJ10


Other interactions of KCNJ10

  • Mutation screening of the three candidate genes CRABP2, GNAT2, and KCNJ10 revealed no disease-associated mutations [14].
  • Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3) [7].
  • K+ channels in the apical membrane of the parietal cell are implicated in the recycling of K+ and, to date, three potential K+ channels (KCNQ1, Kir2.1 and Kir4.1) have been identified [15].
  • Nortriptyline (3-300 muM) reversibly inhibited Kir4.1 currents in a concentration-dependent manner, whereas it marginally affected neuronal Kir2.1 currents [16].
  • 1. In normal brain tissue, AQP4 and Kir4.1 were detected around the microvessels [13].

Analytical, diagnostic and therapeutic context of KCNJ10

  • Western blot analysis using specific antibodies revealed that Kir4.1 and Kir5.1 proteins were expressed in kidney and brain, but co-immunoprecipitated only from kidney [17].
  • We examined the effects of nortriptyline, a tricyclic antidepressant (TCA), on Kir4.1 channel currents heterologously expressed in HEK293T cells, using a whole-cell patch-clamp technique [16].
  • RT-PCR revealed molecular identities of mRNAs for the functional ionic currents, including Kir1.2 for IKir, Kv1.1, Kv1.6, and Kv2.1 for IKDR, and Nav1.5 for INa.TTXR [18].
  • Using real-time PCR, we found that the mRNAs for AQP4 and Kir4.1 are downregulated in retinas that were obtained from patients with proliferative retinopathy compared with post-mortem controls [19].


  1. Supportive evidence for an allelic association of the human KCNJ10 potassium channel gene with idiopathic generalized epilepsy. Lenzen, K.P., Heils, A., Lorenz, S., Hempelmann, A., Höfels, S., Lohoff, F.W., Schmitz, B., Sander, T. Epilepsy Res. (2005) [Pubmed]
  2. Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low- and high-grade human brain tumors. Warth, A., Mittelbronn, M., Wolburg, H. Acta Neuropathol. (2005) [Pubmed]
  3. Identification of a heteromeric interaction that influences the rectification, gating, and pH sensitivity of Kir4.1/Kir5.1 potassium channels. Casamassima, M., D'Adamo, M.C., Pessia, M., Tucker, S.J. J. Biol. Chem. (2003) [Pubmed]
  4. Surface expression of inward rectifier potassium channels is controlled by selective Golgi export. Stockklausner, C., Klocker, N. J. Biol. Chem. (2003) [Pubmed]
  5. Molecular analysis of KCNJ10 on 1q as a candidate gene for Type 2 diabetes in Pima Indians. Farook, V.S., Hanson, R.L., Wolford, J.K., Bogardus, C., Prochazka, M. Diabetes (2002) [Pubmed]
  6. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Buono, R.J., Lohoff, F.W., Sander, T., Sperling, M.R., O'Connor, M.J., Dlugos, D.J., Ryan, S.G., Golden, G.T., Zhao, H., Scattergood, T.M., Berrettini, W.H., Ferraro, T.N. Epilepsy Res. (2004) [Pubmed]
  7. Cloning and characterization of two K+ inward rectifier (Kir) 1.1 potassium channel homologs from human kidney (Kir1.2 and Kir1.3). Shuck, M.E., Piser, T.M., Bock, J.H., Slightom, J.L., Lee, K.S., Bienkowski, M.J. J. Biol. Chem. (1997) [Pubmed]
  8. Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90. Horio, Y., Hibino, H., Inanobe, A., Yamada, M., Ishii, M., Tada, Y., Satoh, E., Hata, Y., Takai, Y., Kurachi, Y. J. Biol. Chem. (1997) [Pubmed]
  9. 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. Fujita, A., Horio, Y., Higashi, K., Mouri, T., Hata, F., Takeguchi, N., Kurachi, Y. J. Physiol. (Lond.) (2002) [Pubmed]
  10. Downregulation of Kir4.1 inward rectifying potassium channel subunits by RNAi impairs potassium transfer and glutamate uptake by cultured cortical astrocytes. Kucheryavykh, Y.V., Kucheryavykh, L.Y., Nichols, C.G., Maldonado, H.M., Baksi, K., Reichenbach, A., Skatchkov, S.N., Eaton, M.J. Glia (2007) [Pubmed]
  11. Glial cell reactivity in a porcine model of retinal detachment. Iandiev, I., Uckermann, O., Pannicke, T., Wurm, A., Tenckhoff, S., Pietsch, U.C., Reichenbach, A., Wiedemann, P., Bringmann, A., Uhlmann, S. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  12. Potassium channels of glial cells: distribution and function. Horio, Y. Jpn. J. Pharmacol. (2001) [Pubmed]
  13. Water transport becomes uncoupled from K+ siphoning in brain contusion, bacterial meningitis, and brain tumours: immunohistochemical case review. Saadoun, S., Papadopoulos, M.C., Krishna, S. J. Clin. Pathol. (2003) [Pubmed]
  14. Novel locus for autosomal recessive cone-rod dystrophy CORD8 mapping to chromosome 1q12-Q24. Khaliq, S., Hameed, A., Ismail, M., Anwar, K., Leroy, B.P., Mehdi, S.Q., Payne, A.M., Bhattacharya, S.S. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  15. Role of potassium in acid secretion. Geibel, J.P. World J. Gastroenterol. (2005) [Pubmed]
  16. Inhibition of astroglial inwardly rectifying kir4.1 channels by a tricyclic antidepressant, nortriptyline. Su, S., Ohno, Y., Lossin, C., Hibino, H., Inanobe, A., Kurachi, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  17. In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1. Tanemoto, M., Kittaka, N., Inanobe, A., Kurachi, Y. J. Physiol. (Lond.) (2000) [Pubmed]
  18. Involvement of Kv1.1 and Nav1.5 in proliferation of gastric epithelial cells. Wu, W.K., Li, G.R., Wong, H.P., Hui, M.K., Tai, E.K., Lam, E.K., Shin, V.Y., Ye, Y.N., Li, P., Yang, Y.H., Luo, J.C., Cho, C.H. J. Cell. Physiol. (2006) [Pubmed]
  19. Diversity of aquaporin mRNA expressed by rat and human retinas. Tenckhoff, S., Hollborn, M., Kohen, L., Wolf, S., Wiedemann, P., Bringmann, A. Neuroreport (2005) [Pubmed]
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