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Gene Review

KCNC1  -  potassium channel, voltage gated Shaw...

Homo sapiens

Synonyms: KV3.1, KV4, Kv3.1, NGK2, Potassium voltage-gated channel subfamily C member 1, ...
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High impact information on KCNC1

  • Here, using mutagenesis and X-ray crystallography, we explore the interaction between Kv4 subunits and KChIP1 [1].
  • Use-dependent unblocking with 4-aminopyridine was not seen for rabbit Ito nor for Kv1.4 currents in Xenopus oocytes, whereas human Ito showed strong use-dependent unblock (as did Kv4 currents) [2].
  • Western blots indicated the presence of Kv4 proteins in both human and rabbit atrial membranes, but Kv1.4 was only detected in the rabbit [2].
  • The most widely distributed K+ channel transcripts in the ferret heart were Kv1.5 (present in 69.3% to 85.6% of myocytes tested, depending on the anatomic region from which myocytes were isolated) and Kv1.4 (46.1% to 93.7%), followed by kv1.2, Kv2.1, and Kv4 [3].
  • Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive K+ current in chemoreceptor cells [4].

Biological context of KCNC1


Anatomical context of KCNC1

  • To operate correctly, Kv4 alpha-subunits in the heart and central nervous system require recently identified beta-subunits of the neuronal calcium sensing protein family called K+ channel-interacting proteins (KChIPs) [9].
  • Residues within the myristoylation motif determine intracellular targeting of the neuronal Ca2+ sensor protein KChIP1 to post-ER transport vesicles and traffic of Kv4 K+ channels [10].
  • The three Ito alpha subunits again showed distinct patterns of distribution: (a) Kv1.4 was localized primarily to the apical portion of the LV septum, LV endocardium, and approximate inner 75% of the LV free wall; (b) Kv4 [11].
  • The localization of the 6 transmembrane domain delayed rectifier channels of the Kv1, Kv2, Kv3 and Kv4 families is given for the retina, the retinal pigment epithelium and the optic nerve [12].
  • Our findings support the hypothesis that Itof is mediated by Kv4-KChIP2 heteromeric ion channels in the great majority of cardiac myocytes [13].

Associations of KCNC1 with chemical compounds

  • These two arginines are conserved in Kv4 subfamily, and alanine replacement of Arg429 and Arg432 in Kv4.2 gave essentially the same results [14].
  • These observations strongly suggest that Kv4 channel gating is tightly coupled to voltage-dependent accessibility changes of native T1 cysteines in the intersubunit Zn(2+) site [15].
  • We performed a lysine-scanning mutagenesis within the proximal 40 amino acid portion and a structure-based mutagenesis in the tetramerization 1 (T1) domain of Kv4 [16].
  • The potential ability of KChIP EF-hands to sense intracellular Ca(2+) levels and transduce these changes to alterations in Kv4 channel inactivation kinetics may serve as a mechanism allowing intracellular Ca(2+) transients to modulate repolarization [17].
  • All members of a given Kv2, Kv3 or Kv4 potassium channel subfamily have identical amino acids at similar positions in their deep pore regions (Thr/Tyr or Thr/Val), which suggests that any difference in surface levels among members is not dictated by these amino acids [18].

Other interactions of KCNC1

  • The four known members of the KCND/Kv4 channel family encode voltage-gated potassium channels [8].

Analytical, diagnostic and therapeutic context of KCNC1

  • In this study, a yeast two-hybrid assay was used to identify inhibitors such as a diaryl-urea compound (CL-888) that binds to and modulates the formation of the Kv4/KChIP complex [19].
  • We examined molecular cloning and functional characterization of novel, fast-inactivating, A-type K(+) channel alpha (Kv4.3L) and beta (KChIP2S) subunits predominantly expressed in mammalian heart and found the sites in Kv4 channels for 1) the regulation of voltage dependency and 2) the CaMKII phosphorylation in the C-terminal cytoplasmic domain [20].


  1. Two N-terminal domains of Kv4 K(+) channels regulate binding to and modulation by KChIP1. Scannevin, R.H., Wang, K., Jow, F., Megules, J., Kopsco, D.C., Edris, W., Carroll, K.C., Lü, Q., Xu, W., Xu, Z., Katz, A.H., Olland, S., Lin, L., Taylor, M., Stahl, M., Malakian, K., Somers, W., Mosyak, L., Bowlby, M.R., Chanda, P., Rhodes, K.J. Neuron (2004) [Pubmed]
  2. Potential molecular basis of different physiological properties of the transient outward K+ current in rabbit and human atrial myocytes. Wang, Z., Feng, J., Shi, H., Pond, A., Nerbonne, J.M., Nattel, S. Circ. Res. (1999) [Pubmed]
  3. In situ hybridization reveals extensive diversity of K+ channel mRNA in isolated ferret cardiac myocytes. Brahmajothi, M.V., Morales, M.J., Liu, S., Rasmusson, R.L., Campbell, D.L., Strauss, H.C. Circ. Res. (1996) [Pubmed]
  4. Viral gene transfer of dominant-negative Kv4 construct suppresses an O2-sensitive K+ current in chemoreceptor cells. Pérez-García, M.T., López-Lppez, J.R., Riesco, A.M., Hoppe, U.C., Marbán, E., Gonzalez, C., Johns, D.C. J. Neurosci. (2000) [Pubmed]
  5. Localization of a highly conserved human potassium channel gene (NGK2-KV4; KCNC1) to chromosome 11p15. Ried, T., Rudy, B., Vega-Saenz de Miera, E., Lau, D., Ward, D.C., Sen, K. Genomics (1993) [Pubmed]
  6. Organization of the region encompassing the human serum amyloid A (SAA) gene family on chromosome 11p15.1. Sellar, G.C., Oghene, K., Boyle, S., Bickmore, W.A., Whitehead, A.S. Genomics (1994) [Pubmed]
  7. Voltage-dependent K+ channel acts as sex steroid sensor in endocrine cells of the human ovary. Kunz, L., Rämsch, R., Krieger, A., Young, K.A., Dissen, G.A., Stouffer, R.L., Ojeda, S.R., Mayerhofer, A. J. Cell. Physiol. (2006) [Pubmed]
  8. Gene structures and expression profiles of three human KCND (Kv4) potassium channels mediating A-type currents I(TO) and I(SA). Isbrandt, D., Leicher, T., Waldschütz, R., Zhu, X., Luhmann, U., Michel, U., Sauter, K., Pongs, O. Genomics (2000) [Pubmed]
  9. Ito channels are octomeric complexes with four subunits of each Kv4.2 and K+ channel-interacting protein 2. Kim, L.A., Furst, J., Butler, M.H., Xu, S., Grigorieff, N., Goldstein, S.A. J. Biol. Chem. (2004) [Pubmed]
  10. Residues within the myristoylation motif determine intracellular targeting of the neuronal Ca2+ sensor protein KChIP1 to post-ER transport vesicles and traffic of Kv4 K+ channels. O'Callaghan, D.W., Hasdemir, B., Leighton, M., Burgoyne, R.D. J. Cell. Sci. (2003) [Pubmed]
  11. Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes. Brahmajothi, M.V., Campbell, D.L., Rasmusson, R.L., Morales, M.J., Trimmer, J.S., Nerbonne, J.M., Strauss, H.C. J. Gen. Physiol. (1999) [Pubmed]
  12. Localization of potassium channels in the retina. Pinto, L.H., Klumpp, D.J. Progress in retinal and eye research. (1998) [Pubmed]
  13. Kv4.2 and KChIP2 transcription in individual cardiomyocytes from the rat left ventricular free wall. Schultz, J.H., Janzen, C., Volk, T., Ehmke, H. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  14. Two arginines in the cytoplasmic C-terminal domain are essential for voltage-dependent regulation of A-type K+ current in the Kv4 channel subfamily. Hatano, N., Ohya, S., Muraki, K., Clark, R.B., Giles, W.R., Imaizumi, Y. J. Biol. Chem. (2004) [Pubmed]
  15. Voltage-dependent gating rearrangements in the intracellular T1-T1 interface of a K+ channel. Wang, G., Covarrubias, M. J. Gen. Physiol. (2006) [Pubmed]
  16. Contribution of N- and C-terminal channel domains to Kv4.2 domains to KChIP interaction [corrected]. Callsen, B., Isbrandt, D., Sauter, K., Hartmann, L.S., Pongs, O., Bähring, R. J. Physiol. (Lond.) (2005) [Pubmed]
  17. Elucidating KChIP effects on Kv4.3 inactivation and recovery kinetics with a minimal KChIP2 isoform. Patel, S.P., Campbell, D.L., Strauss, H.C. J. Physiol. (Lond.) (2002) [Pubmed]
  18. Amino acids in the pore region of Kv1 potassium channels dictate cell-surface protein levels: a possible trafficking code in the Kv1 subfamily. Zhu, J., Gomez, B., Watanabe, I., Thornhill, W.B. Biochem. J. (2005) [Pubmed]
  19. Identification and characterization of small molecule modulators of KChIP/Kv4 function. Bowlby, M.R., Chanda, P., Edris, W., Hinson, J., Jow, F., Katz, A.H., Kennedy, J., Krishnamurthy, G., Pitts, K., Ryan, K., Zhang, H., Greenblatt, L. Bioorg. Med. Chem. (2005) [Pubmed]
  20. Molecular pharmacological studies on potassium channels and their regulatory molecules. Ohya, S. Yakugaku Zasshi (2006) [Pubmed]
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