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Gene Review

KCNJ8  -  potassium channel, inwardly rectifying...

Homo sapiens

Synonyms: ATP-sensitive inward rectifier potassium channel 8, Inward rectifier K(+) channel Kir6.1, KIR6.1, Kir6.1, Potassium channel, inwardly rectifying subfamily J member 8, ...
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Disease relevance of KCNJ8


High impact information on KCNJ8


Biological context of KCNJ8


Anatomical context of KCNJ8

  • These findings, taken together with the electrophysiological results, suggest that K(ATP) channel in corporal smooth muscle cells is composed of heteromultimers of Kir6.1 and Kir6.2 with the ratio of 3 : 1 or 4 : 0 and SUR2B [11].
  • K ATP channels of primary human coronary artery endothelial cells consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits [12].
  • Recently, we have isolated a KATP channel cDNA (uKATP-1) that is expressed ubiquitously in rat tissues including pancreatic islets, pituitary, skeletal muscle, and heart [7].
  • Our results indicate that the major K(ATP) channel expressed in human myometrium is composed of Kir6.1 and SUR2B, and that down-regulation of this channel may facilitate myometrial function during late pregnancy [13].
  • ROMK1 and KAB-2 are characterized with a Walker type-A ATP-binding motif in their carboxyl termini, and may be involved in K+ transport in renal epithelial and brain glial cells. uKATP-1 and BIR form with sulfonylurea receptors, the so-called ATP-sensitive K+ channels [14].

Associations of KCNJ8 with chemical compounds

  • Although pinacidil is a nonselective activator of expressed sK(ATP) channels, diazoxide did not open channels formed by Kir6.1/SUR2A, Kir6.2/SUR2A (known components of cardiac sK(ATP) channels) or Kir6.2/SUR2B [15].
  • P-1075 activated all the K(ATP) channels, except Kir6.1/SUR1 channels [15].
  • In whole cells, the recombinant vascular K(ATP) channel, Kir6.1/SUR2B, was inhibited by HMR 1883 and glibenclamide with IC(50) values of 5.3 and 0.043 microM, respectively [16].
  • Tempol also abolished the stimulatory effect of 30 muM nicotine on Kir6.1 currents [17].
  • This inward current was significantly inhibited by PNU-37883A and by a specific anti-Kir6.1 antibody [17].

Physical interactions of KCNJ8

  • However, until now the existence of such heteromultimeric Kir6.1/Kir6.2 complexes has not been demonstrated for native K(ATP) channels [12].
  • This discovery may help design specific agents to selectively modulate the function of Kir6.1/SUR1 channel complex and facilitate the understanding of the structure-function relationship of specific subtype of K(ATP) channels [18].

Other interactions of KCNJ8

  • Our results demonstrate that mitoK(ATP) channels closely resemble Kir6.1/SUR1 sK(ATP) channels in their pharmacological profiles [15].
  • They also increased the levels of SUR2 and Kir6.2 (P<0.01), but had no effect on the level of Kir6.1 (P>0.05) [19].
  • Urocortin-mediated cardioprotection involves several mechanisms, including increased expression of Kir6.1 K(ATP) channels and HSP90, although other as yet poorly understood mechanisms have also been implicated [20].
  • KV2.1, BKCa, KIR6.1, and TASK1 were all demonstrated at the protein level [21].

Analytical, diagnostic and therapeutic context of KCNJ8


  1. Molecular characterization of a local sulfonylurea system in human adipose tissue. Gabrielsson, B.G., Karlsson, A.C., Lönn, M., Olofsson, L.E., Johansson, J.M., Torgerson, J.S., Sjöström, L., Carlsson, B., Edén, S., Carlsson, L.M. Mol. Cell. Biochem. (2004) [Pubmed]
  2. Roles of ATP-sensitive K+ channels as metabolic sensors: studies of Kir6.x null mice. Minami, K., Miki, T., Kadowaki, T., Seino, S. Diabetes (2004) [Pubmed]
  3. Physiology and pathophysiology of K(ATP) channels in the pancreas and cardiovascular system: a review. Seino, S. J. Diabetes Complicat. (2003) [Pubmed]
  4. Gene knockout of the KCNJ8-encoded Kir6.1 K(ATP) channel imparts fatal susceptibility to endotoxemia. Kane, G.C., Lam, C.F., O'Cochlain, F., Hodgson, D.M., Reyes, S., Liu, X.K., Miki, T., Seino, S., Katusic, Z.S., Terzic, A. FASEB J. (2006) [Pubmed]
  5. Mouse model of Prinzmetal angina by disruption of the inward rectifier Kir6.1. Miki, T., Suzuki, M., Shibasaki, T., Uemura, H., Sato, T., Yamaguchi, K., Koseki, H., Iwanaga, T., Nakaya, H., Seino, S. Nat. Med. (2002) [Pubmed]
  6. Extracellular links in Kir subunits control the unitary conductance of SUR/Kir6.0 ion channels. Repunte, V.P., Nakamura, H., Fujita, A., Horio, Y., Findlay, I., Pott, L., Kurachi, Y. EMBO J. (1999) [Pubmed]
  7. cDNA sequence, gene structure, and chromosomal localization of the human ATP-sensitive potassium channel, uKATP-1, gene (KCNJ8). Inagaki, N., Inazawa, J., Seino, S. Genomics (1995) [Pubmed]
  8. Genomic organization and expression of KCNJ8/Kir6.1, a gene encoding a subunit of an ATP-sensitive potassium channel. Erginel-Unaltuna, N., Yang, W.P., Blanar, M.A. Gene (1998) [Pubmed]
  9. Cytoplasmic terminus domains of Kir6.x confer different nucleotide-dependent gating on the ATP-sensitive K+ channel. Takano, M., Xie, L.H., Otani, H., Horie, M. J. Physiol. (Lond.) (1998) [Pubmed]
  10. Block of human aorta Kir6.1 by the vascular KATP channel inhibitor U37883A. Surah-Narwal, S., Xu, S.Z., McHugh, D., McDonald, R.L., Hough, E., Cheong, A., Partridge, C., Sivaprasadarao, A., Beech, D.J. Br. J. Pharmacol. (1999) [Pubmed]
  11. Molecular basis and characteristics of KATP channel in human corporal smooth muscle cells. Insuk, S.O., Chae, M.R., Choi, J.W., Yang, D.K., Sim, J.H., Lee, S.W. Int. J. Impot. Res. (2003) [Pubmed]
  12. K ATP channels of primary human coronary artery endothelial cells consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits. Yoshida, H., Feig, J.E., Morrissey, A., Ghiu, I.A., Artman, M., Coetzee, W.A. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  13. Expression of mRNA transcripts for ATP-sensitive potassium channels in human myometrium. Curley, M., Cairns, M.T., Friel, A.M., McMeel, O.M., Morrison, J.J., Smith, T.J. Mol. Hum. Reprod. (2002) [Pubmed]
  14. Inwardly rectifying potassium channels: their molecular heterogeneity and function. Isomoto, S., Kondo, C., Kurachi, Y. Jpn. J. Physiol. (1997) [Pubmed]
  15. Pharmacological comparison of native mitochondrial K(ATP) channels with molecularly defined surface K(ATP) channels. Liu, Y., Ren, G., O'Rourke, B., Marbán, E., Seharaseyon, J. Mol. Pharmacol. (2001) [Pubmed]
  16. Interaction of the sulfonylthiourea HMR 1833 with sulfonylurea receptors and recombinant ATP-sensitive K(+) channels: comparison with glibenclamide. Russ, U., Lange, U., Löffler-Walz, C., Hambrock, A., Quast, U. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  17. Mediation of the effect of nicotine on Kir6.1 channels by superoxide anion production. Hanna, S.T., Cao, K., Sun, X., Wang, R. J. Cardiovasc. Pharmacol. (2005) [Pubmed]
  18. Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells. Jiang, B., Cao, K., Wang, R. Eur. J. Pharmacol. (2004) [Pubmed]
  19. Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion. Zhao, J.L., Yang, Y.J., You, S.J., Jing, Z.C., Wu, Y.J., Cheng, J.L., Gao, R.L. Coron. Artery Dis. (2006) [Pubmed]
  20. Urocortins: take them to heart. Scarabelli, T., Knight, R. Current medicinal chemistry. Cardiovascular and hematological agents. (2004) [Pubmed]
  21. Expression and function of potassium channels in the human placental vasculature. Wareing, M., Bai, X., Seghier, F., Turner, C.M., Greenwood, S.L., Baker, P.N., Taggart, M.J., Fyfe, G.K. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
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