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Gene Review

Kcnb1  -  potassium channel, voltage gated Shab...

Rattus norvegicus

Synonyms: DRK1, DRK1PC, Delayed rectifier potassium channel 1, Kcr1-1, Kv2.1, ...
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Disease relevance of Kcnb1

  • Here we provide evidence that the localization and function of Kv2.1, the major somatodendritic delayed rectifier voltage-dependent K+ channel in central neurons, is regulated by hypoxia/ischemia-induced changes in metabolic state and intracellular Ca2+ levels [1].
  • Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia [1].
  • T4 administration induced hyperthyroidism and cardiac hypertrophy, and it increased the Kv1.5 and Kv2.1 mRNA levels over the control value (212% and 140%, respectively; n = 6, p < 0.05) [2].
  • The amounts of Kv1.2 and Kv2.1 mRNA were markedly lower in DOCA-salt treated rats (66%) than in sham-DOCA rats, but no effect was observed after stenosis [3].
  • A chimeric protein containing the hemagglutinin protein from influenza virus and the region of Kv2.1 that differentiates the two truncation mutants (amino acids 536-666) was also expressed in MDCK cells, where it was found in high density clusters similar to those observed for Kv2 [4].

Psychiatry related information on Kcnb1


High impact information on Kcnb1

  • Using in vitro transcripts made from a directional complementary DNA library we have isolated, by expression cloning in Xenopus oocytes, a novel K+-channel gene (drk1) [7].
  • Structurally, drk1 encodes an amino-acid sequence which is more closely related to the Drosophila Shab gene than to the Shaker gene [7].
  • Our finding that neuronal activity modifies the phosphorylation state, localization and function of Kv2.1 suggests an important link between excitatory neurotransmission and the intrinsic excitability of pyramidal neurons [8].
  • Voltage-dependent Kv2.1 K(+) channels, which mediate delayed rectifier Kv currents (I(K)), are expressed in large clusters on the somata and dendrites of principal pyramidal neurons, where they regulate neuronal excitability [8].
  • 1. In cultured rat hippocampal pyramidal neurons, glutamate stimulation rapidly causes dephosphorylation of Kv2.1, translocation of Kv2.1 from clusters to a more uniform localization, and a shift in the voltage-dependent activation of I(K) [8].

Chemical compound and disease context of Kcnb1


Biological context of Kcnb1

  • Together, these results indicate that Tyr(124) is a significant site at which the mutually antagonistic activities of Src and cyt-PTPepsilon affect Kv2.1 phosphorylation and activity [10].
  • Disruption of pancreatic beta-cell lipid rafts modifies Kv2.1 channel gating and insulin exocytosis [11].
  • Voltage-gated potassium channels responsible for the delayed rectifier current, including Kv2.1, are usually assigned roles in the repolarization of the action potential [12].
  • Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels [13].
  • SNAP-25 C-terminal domains, SNAP-25(198-206) and SNAP-25(181-197), had no effect on Kv2.1 gating kinetics [14].

Anatomical context of Kcnb1

  • The voltage-gated delayed-rectifier-type K+ channel Kv2.1 is expressed in high-density clusters on the soma and proximal dendrites of mammalian central neurons; thus, dynamic regulation of Kv2.1 would be predicted to have an impact on dendritic excitability [15].
  • A specific antibody against Kv2.1 channel subunits was used to determine the surface distribution and clustering of Kv2.1 subunit-containing channels in the cell membrane of alpha-motoneurones and other spinal cord neurones [12].
  • Voltage-activated Kv2.1 channels have properties commensurate with a contribution to delayed rectifier currents and are expressed in neurones throughout the mammalian central nervous system [12].
  • The properties of neuronal Kv2.1 are recapitulated in recombinant Kv2.1 expressed in human embryonic kidney 293 (HEK293) cells, but not COS-1 cells, because of cell background-specific differences in Kv2.1 phosphorylation [16].
  • Here we report a biochemical characterization of Kv2.1 channel complexes from both recombinant cell lines and native rat brain [17].

Associations of Kcnb1 with chemical compounds

  • In the present study, we identify tyrosine 124 within the T1 cytosolic domain of Kv2.1 as a target site for the activities of Src and cyt-PTPepsilon [10].
  • Rat brain Kv2.1 polypeptides are phosphorylated extensively, leading to a dramatically increased molecular mass on sodium dodecyl sulfate gels [15].
  • Phosphoamino acid analysis of Kv2.1 expressed in transfected cells and labeled in vivo with 32P shows that phosphorylation was restricted to serine residues and that a truncation mutant, DeltaC318, which lacks the last 318 amino acids in the cytoplasmic carboxyl terminus, was phosphorylated to a much lesser degree than was wild-type Kv2 [15].
  • The present study suggests that, in beta-cells, Kv2.1 channels mediate a fast-inactivating K(+) current at physiological temperatures and may be regulated by the metabolic generation of NADPH [18].
  • The Kv2.1/Kv9.3 heteromer generates an O2 sensitive potassium channel and induces a slow deactivation that has important consequences for brain and lung physiology [19].

Enzymatic interactions of Kcnb1

  • Tyr(124) is phosphorylated by Src in vitro; in whole cells, Y124F Kv2.1 is significantly less phosphorylated by Src and loses most of its ability to bind the D245A substrate-trapping mutant of cyt-PTPepsilon [10].

Regulatory relationships of Kcnb1

  • These properties are consistent with the hypothesis that the rapidly deactivating current is attributable to Kv3.1/3.2 channels and the slowly deactivating current to Kv2.1-containing channels [20].

Other interactions of Kcnb1

  • 1. Anti-Kv1.5 and anti-Kv2.1 caused additive depolarization in resistance PASMCs (Kv1.5>Kv2.1) and inhibited hypoxic depolarization [21].
  • Kv2.1 and KChAP were coimmunoprecipitated from in vitro translation reactions supporting a direct interaction between the two proteins [22].
  • Kv2.1 and Kv4.2 were not affected by T3 or PTU. mRNA of erg was not affected by T3 in the atrium but decreased in the ventricle (P < 0.01) [23].
  • This study establishes that Kv2 and 1 channel homologs mediate the majority of repolarizing delayed rectifier current in rat beta-cells and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes [24].
  • The protein expression of Kv2.1, Kv1.4, and Kv4.2 was detected by using Western blotting [5].

Analytical, diagnostic and therapeutic context of Kcnb1


  1. Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia. Misonou, H., Mohapatra, D.P., Menegola, M., Trimmer, J.S. J. Neurosci. (2005) [Pubmed]
  2. Effects of thyroid status on expression of voltage-gated potassium channels in rat left ventricle. Nishiyama, A., Kambe, F., Kamiya, K., Seo, H., Toyama, J. Cardiovasc. Res. (1998) [Pubmed]
  3. Ventricular hypertrophy induced by mineralocorticoid treatment or aortic stenosis differentially regulates the expression of cardiac K+ channels in the rat. Capuano, V., Ruchon, Y., Antoine, S., Sant, M.C., Renaud, J.F. Mol. Cell. Biochem. (2002) [Pubmed]
  4. Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. Scannevin, R.H., Murakoshi, H., Rhodes, K.J., Trimmer, J.S. J. Cell Biol. (1996) [Pubmed]
  5. Messenger RNA and protein expression analysis of voltage-gated potassium channels in the brain of Abeta(25-35)-treated rats. Pan, Y., Xu, X., Tong, X., Wang, X. J. Neurosci. Res. (2004) [Pubmed]
  6. Delayed rectifier potassium currents and Kv2.1 mRNA increase in hippocampal neurons of scopolamine-induced memory-deficient rats. Zhong, C.B., Pan, Y.P., Tong, X.Y., Xu, X.H., Wang, X.L. Neurosci. Lett. (2005) [Pubmed]
  7. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Frech, G.C., VanDongen, A.M., Schuster, G., Brown, A.M., Joho, R.H. Nature (1989) [Pubmed]
  8. Regulation of ion channel localization and phosphorylation by neuronal activity. Misonou, H., Mohapatra, D.P., Park, E.W., Leung, V., Zhen, D., Misonou, K., Anderson, A.E., Trimmer, J.S. Nat. Neurosci. (2004) [Pubmed]
  9. The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies. Michelakis, E.D., McMurtry, M.S., Sonnenberg, B., Archer, S.L. Adv. Exp. Med. Biol. (2003) [Pubmed]
  10. Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase epsilon. Tiran, Z., Peretz, A., Attali, B., Elson, A. J. Biol. Chem. (2003) [Pubmed]
  11. Disruption of pancreatic beta-cell lipid rafts modifies Kv2.1 channel gating and insulin exocytosis. Xia, F., Gao, X., Kwan, E., Lam, P.P., Chan, L., Sy, K., Sheu, L., Wheeler, M.B., Gaisano, H.Y., Tsushima, R.G. J. Biol. Chem. (2004) [Pubmed]
  12. Focal aggregation of voltage-gated, Kv2.1 subunit-containing, potassium channels at synaptic sites in rat spinal motoneurones. Muennich, E.A., Fyffe, R.E. J. Physiol. (Lond.) (2004) [Pubmed]
  13. Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels. Pal, S., Hartnett, K.A., Nerbonne, J.M., Levitan, E.S., Aizenman, E. J. Neurosci. (2003) [Pubmed]
  14. Modulation of Kv2.1 channel gating and TEA sensitivity by distinct domains of SNAP-25. He, Y., Kang, Y., Leung, Y.M., Xia, F., Gao, X., Xie, H., Gaisano, H.Y., Tsushima, R.G. Biochem. J. (2006) [Pubmed]
  15. Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Murakoshi, H., Shi, G., Scannevin, R.H., Trimmer, J.S. Mol. Pharmacol. (1997) [Pubmed]
  16. The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation-dependent localization, voltage-dependent gating, and muscarinic modulation to diverse Kv channels. Mohapatra, D.P., Trimmer, J.S. J. Neurosci. (2006) [Pubmed]
  17. Biochemical characterization of the native Kv2.1 potassium channel. Chung, J.J., Li, M. FEBS J. (2005) [Pubmed]
  18. Temperature and redox state dependence of native Kv2.1 currents in rat pancreatic beta-cells. MacDonald, P.E., Salapatek, A.M., Wheeler, M.B. J. Physiol. (Lond.) (2003) [Pubmed]
  19. Different Kv2.1/Kv9.3 heteromer expression during brain and lung post-natal development in the rat. Coma, M., Vicente, R., Tsevi, I., Grande, M., Tamkun, M.M., Felipe, A. Journal of physiology and biochemistry. (2002) [Pubmed]
  20. Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels. Baranauskas, G., Tkatch, T., Surmeier, D.J. J. Neurosci. (1999) [Pubmed]
  21. Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Archer, S.L., Wu, X.C., Thébaud, B., Nsair, A., Bonnet, S., Tyrrell, B., McMurtry, M.S., Hashimoto, K., Harry, G., Michelakis, E.D. Circ. Res. (2004) [Pubmed]
  22. Cloning and expression of a novel K+ channel regulatory protein, KChAP. Wible, B.A., Yang, Q., Kuryshev, Y.A., Accili, E.A., Brown, A.M. J. Biol. Chem. (1998) [Pubmed]
  23. Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats. Ma, M.L., Watanabe, K., Watanabe, H., Hosaka, Y., Komura, S., Aizawa, Y., Yamamoto, T. Japanese heart journal. (2003) [Pubmed]
  24. Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. MacDonald, P.E., Ha, X.F., Wang, J., Smukler, S.R., Sun, A.M., Gaisano, H.Y., Salapatek, A.M., Backx, P.H., Wheeler, M.B. Mol. Endocrinol. (2001) [Pubmed]
  25. Molecular basis of voltage-dependent delayed rectifier K+ channels in smooth muscle cells from rat tail artery. Xu, C., Tang, G., Lu, Y., Wang, R. Life Sci. (2000) [Pubmed]
  26. Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Xu, C., Lu, Y., Tang, G., Wang, R. Am. J. Physiol. (1999) [Pubmed]
  27. Gene transfer and metabolic modulators as new therapies for pulmonary hypertension. Increasing expression and activity of potassium channels in rat and human models. Michelakis, E.D., Dyck, J.R., McMurtry, M.S., Wang, S., Wu, X.C., Moudgil, R., Hashimoto, K., Puttagunta, L., Archer, S.L. Adv. Exp. Med. Biol. (2001) [Pubmed]
  28. Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain. Trimmer, J.S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  29. Modulation of outward potassium currents in aligned cultures of neonatal rat ventricular myocytes during phorbol ester-induced hypertrophy. Walsh, K.B., Sweet, J.K., Parks, G.E., Long, K.J. J. Mol. Cell. Cardiol. (2001) [Pubmed]
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