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Gene Review

Kcnc1  -  potassium voltage gated channel, Shaw...

Mus musculus

Synonyms: C230009H10Rik, KShIIIB, KV4, Kcr2-1, Kv3.1, ...
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Disease relevance of Kcnc1


Psychiatry related information on Kcnc1

  • The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327) [5].
  • In spite of the severe motor impairment, Kv3.1/Kv3.3-deficient mice are hyperactive, show increased exploratory activity, and display no obvious learning or memory deficit [2].
  • In a test for coordinated motor skill, however, homozygous Kv3.1-/- mice perform significantly worse than their heterozygous Kv3.1+/- or wild-type littermates [3].

High impact information on Kcnc1

  • The use of P388D1 cells, an alpha 6-integrin deficient macrophage cell line, facilitated this analysis because expression of either the alpha 6A or alpha 6B subunit cDNAs restores their activation responsive laminin adhesion (Shaw, L. S., M. Lotz, and A. M. Mercurio. 1993. J. Biol. Chem. 268:11401-11408) [6].
  • The alpha 6 beta 1 integrin is expressed on the macrophage surface in an inactive state and requires cellular activation with PMA or cytokines to function as a laminin receptor (Shaw, L. M., J. M. Messier, and A. M. Mercurio. 1990. J. Cell Biol. 110:2167-2174) [6].
  • Macrophages require activation with either PMA (Mercurio, A. M., and L. M. Shaw. 1988. J. Cell Biol. 107:1873-1880) or interferon-gamma (Shaw, L. M., and A. M. Mercurio. 1989. J. Exp. Med. 169:303-308) to adhere to a laminin substratum [7].
  • The Kv4 A-type potassium currents contribute to controlling the frequency of slow repetitive firing and back-propagation of action potentials in neurons and shape the action potential in heart [8].
  • Both fast and slow skeletal muscles of Kv3.1-/- mice are slower to reach peak force and to relax after contraction, consequently leading to tetanic responses at lower stimulation frequencies [3].

Biological context of Kcnc1

  • Localization of Shaw-related K+ channel genes on mouse and human chromosomes [9].
  • 3. The presence of Kv4 channels at GABAergic synapses would be expected to weaken inhibition during dendritic depolarization by backpropagating action potentials [10].
  • The graded penetrance of mutant traits appears to depend on the number of null alleles, suggesting that some of the distinct phenotypic traits visible in the absence of Kv3.1 and Kv3.3 K(+) channels are unrelated and may be caused by localized dysfunction in different brain regions [2].
  • Although their kinetics and cell surface expression are regulated by auxiliary subunits, little is known about the proteins that may interact with Kv4 during development [11].
  • Kv4 channels represent the main class of brain A-type K+ channels that operate in the subthreshold range of membrane potentials (Serodio, P., E. Vega-Saenz de Miera, and B. Rudy. 1996. J. Neurophysiol. 75:2174- 2179), and their function depends critically on inactivation gating [12].

Anatomical context of Kcnc1


Associations of Kcnc1 with chemical compounds

  • Here, we used immunolabeling with specific antibodies against Kv4.2 and Kv4.3, in combination with GABA immunogold staining, to determine the cellular, subcellular, and synaptic localization of Kv4 channels in the primary visual cortex of mice, in which subsets of pyramidal cells express yellow fluorescent protein [10].
  • Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans [16].
  • These results conclusively demonstrate that the T1--T1 interface of Kv4 channels is functionally active and dynamic, and that critical reactive thiolate groups in this interface may not be protected by Zn(2+) binding [17].
  • 5. The amplitude of Kv3.1 currents, and the probability of channel openings, was reduced by a phorbol ester activator of protein kinase C, and the action of this agent was blocked by preincubation with the protein kinase inhibitor H7 (1-[5-isoquinolinesulfonyl]-2-methyl piperazine) [18].
  • Low tetraethylammonium (TEA) concentrations (</=1 mM), which block only a few known K(+) channels including Kv3.1-Kv3.2, profoundly impaired action potential repolarization and high-frequency firing [19].

Enzymatic interactions of Kcnc1


Regulatory relationships of Kcnc1

  • Although the techniques employed in this study detect mRNA and not protein, it can be inferred from the differential distribution of Kv4 transcripts that CN neurons selectively regulate the expression of Shal K(+) channels among individual neurons throughout development [21].

Other interactions of Kcnc1

  • We found that the expression level, and cellular and subcellular distribution of the other prominent brain Kv4 family member Kv4.3, was indistinguishable between WT and Kv4.2(-/-) samples [22].
  • The Kv3.1 gene maps to human chromosome 11; the related Kv1.1 and Kv3.2 genes are localized on human chromosome 12, while the IsK gene maps to human chromosome 21 [1].
  • Quantitative PCR indicated that in colonic and jejunal tissue, Kv4.3 transcripts demonstrate greater relative abundance than transcripts encoding Kv4.1 or Kv4 [15].
  • Contribution of Kv4 channels toward the A-type potassium current in murine colonic myocytes [15].
  • Substitution of linkers from the slowly activating Shab and Shaw channels resulted in a three-to fourfold slowing of activation and deactivation [23].

Analytical, diagnostic and therapeutic context of Kcnc1

  • A yeast two-hybrid assay demonstrated that the last 22 amino acids of the PPTX C terminus interact with the N terminus of Kv4 [11].
  • Transcripts encoding Kv4 channels were detected in isolated antral myocytes by RT-PCR [24].
  • Electroencephalographic (EEG) recordings from homozygous Kv3.1(-/-) mice show a three- to fourfold increase in both absolute and relative spectral power in the gamma frequency range (20-60 Hz) [25].
  • In situ hybridization of Kv3.1 mRNA demonstrated that the gene was expressed at high levels in the external granule layer (EGL) as well as in the internal granule layer (IGL) at all postnatal stages (P) examined (from P3 to P10) [26].
  • Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites [27].


  1. The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells. Grissmer, S., Ghanshani, S., Dethlefs, B., McPherson, J.D., Wasmuth, J.J., Gutman, G.A., Cahalan, M.D., Chandy, K.G. J. Biol. Chem. (1992) [Pubmed]
  2. Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. Espinosa, F., McMahon, A., Chan, E., Wang, S., Ho, C.S., Heintz, N., Joho, R.H. J. Neurosci. (2001) [Pubmed]
  3. Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures. Ho, C.S., Grange, R.W., Joho, R.H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Functional knockout of the transient outward current, long-QT syndrome, and cardiac remodeling in mice expressing a dominant-negative Kv4 alpha subunit. Barry, D.M., Xu, H., Schuessler, R.B., Nerbonne, J.M. Circ. Res. (1998) [Pubmed]
  5. Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice. Joho, R.H., Street, C., Matsushita, S., Knöpfel, T. Genes Brain Behav. (2006) [Pubmed]
  6. Regulation of alpha 6 beta 1 integrin laminin receptor function by the cytoplasmic domain of the alpha 6 subunit. Shaw, L.M., Mercurio, A.M. J. Cell Biol. (1993) [Pubmed]
  7. The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin. Shaw, L.M., Messier, J.M., Mercurio, A.M. J. Cell Biol. (1990) [Pubmed]
  8. Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain. Holmqvist, M.H., Cao, J., Hernandez-Pineda, R., Jacobson, M.D., Carroll, K.I., Sung, M.A., Betty, M., Ge, P., Gilbride, K.J., Brown, M.E., Jurman, M.E., Lawson, D., Silos-Santiago, I., Xie, Y., Covarrubias, M., Rhodes, K.J., Distefano, P.S., An, W.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  9. Localization of Shaw-related K+ channel genes on mouse and human chromosomes. Haas, M., Ward, D.C., Lee, J., Roses, A.D., Clarke, V., D'Eustachio, P., Lau, D., Vega-Saenz de Miera, E., Rudy, B. Mamm. Genome (1993) [Pubmed]
  10. Differential Expression of IA Channel Subunits Kv4.2 and Kv4.3 in Mouse Visual Cortical Neurons and Synapses. Burkhalter, A., Gonchar, Y., Mellor, R.L., Nerbonne, J.M. J. Neurosci. (2006) [Pubmed]
  11. A secretory-type protein, containing a pentraxin domain, interacts with an A-type K+ channel. Duzhyy, D., Harvey, M., Sokolowski, B. J. Biol. Chem. (2005) [Pubmed]
  12. Inactivation gating of Kv4 potassium channels: molecular interactions involving the inner vestibule of the pore. Jerng, H.H., Shahidullah, M., Covarrubias, M. J. Gen. Physiol. (1999) [Pubmed]
  13. Differential expression of voltage-gated potassium channel genes in auditory nuclei of the mouse brainstem. Grigg, J.J., Brew, H.M., Tempel, B.L. Hear. Res. (2000) [Pubmed]
  14. Modulation of Kv4-encoded K(+) currents in the mammalian myocardium by neuronal calcium sensor-1. Guo, W., Malin, S.A., Johns, D.C., Jeromin, A., Nerbonne, J.M. J. Biol. Chem. (2002) [Pubmed]
  15. Contribution of Kv4 channels toward the A-type potassium current in murine colonic myocytes. Amberg, G.C., Koh, S.D., Hatton, W.J., Murray, K.J., Monaghan, K., Horowitz, B., Sanders, K.M. J. Physiol. (Lond.) (2002) [Pubmed]
  16. Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans. Fawcett, G.L., Santi, C.M., Butler, A., Harris, T., Covarrubias, M., Salkoff, L. J. Biol. Chem. (2006) [Pubmed]
  17. Functionally active t1-t1 interfaces revealed by the accessibility of intracellular thiolate groups in kv4 channels. Wang, G., Shahidullah, M., Rocha, C.A., Strang, C., Pfaffinger, P.J., Covarrubias, M. J. Gen. Physiol. (2005) [Pubmed]
  18. Electrophysiological and pharmacological characterization of a mammalian Shaw channel expressed in NIH 3T3 fibroblasts. Kanemasa, T., Gan, L., Perney, T.M., Wang, L.Y., Kaczmarek, L.K. J. Neurophysiol. (1995) [Pubmed]
  19. Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons. Erisir, A., Lau, D., Rudy, B., Leonard, C.S. J. Neurophysiol. (1999) [Pubmed]
  20. Input-specific immunolocalization of differentially phosphorylated Kv4.2 in the mouse brain. Varga, A.W., Anderson, A.E., Adams, J.P., Vogel, H., Sweatt, J.D. Learn. Mem. (2000) [Pubmed]
  21. Expression of Shal potassium channel subunits in the adult and developing cochlear nucleus of the mouse. Fitzakerley, J.L., Star, K.V., Rinn, J.L., Elmquist, B.J. Hear. Res. (2000) [Pubmed]
  22. Unanticipated Region- and Cell-Specific Downregulation of Individual KChIP Auxiliary Subunit Isotypes in Kv4.2 Knock-Out Mouse Brain. Menegola, M., Trimmer, J.S. J. Neurosci. (2006) [Pubmed]
  23. Role of the S3-S4 linker in Shaker potassium channel activation. Mathur, R., Zheng, J., Yan, Y., Sigworth, F.J. J. Gen. Physiol. (1997) [Pubmed]
  24. Characterization of the A-type potassium current in murine gastric antrum. Amberg, G.C., Baker, S.A., Koh, S.D., Hatton, W.J., Murray, K.J., Horowitz, B., Sanders, K.M. J. Physiol. (Lond.) (2002) [Pubmed]
  25. Increased gamma- and decreased delta-oscillations in a mouse deficient for a potassium channel expressed in fast-spiking interneurons. Joho, R.H., Ho, C.S., Marks, G.A. J. Neurophysiol. (1999) [Pubmed]
  26. Expression of Kv3.1 and Kv4.2 genes in developing cerebellar granule cells. Shibata, R., Wakazono, Y., Nakahira, K., Trimmer, J.S., Ikenaka, K. Dev. Neurosci. (1999) [Pubmed]
  27. A unique role for Kv3 voltage-gated potassium channels in starburst amacrine cell signaling in mouse retina. Ozaita, A., Petit-Jacques, J., Völgyi, B., Ho, C.S., Joho, R.H., Bloomfield, S.A., Rudy, B. J. Neurosci. (2004) [Pubmed]
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