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Kcna4  -  potassium channel, voltage gated shaker...

Rattus norvegicus

Synonyms: KCHAN, Kv1.4, Kv4, Potassium voltage-gated channel subfamily A member 4, RCK4, ...
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Disease relevance of Kcna4

  • These results indicate that renovascular hypertension causes specific reductions in Kv4 subfamily channel mRNA expression and that this effect is likely to be mediated primarily by an increase in cardiac afterload [1].
  • Chronic administration of captopril, an angiotensin-converting enzyme inhibitor, blocked the development of hypertension and the suppression of Kv4 subfamily channel mRNA expression in 2K-1C rats [1].
  • However, the steady-state amount of Kv4 mRNA was even lower in rats with DOCA-salt-induced hypertrophy than in those with stenosis-induced ventricular hypertrophy [2].
  • During the active myocarditis phase, the effective refractory period (ERP), the duration of the monophasic action potential (MAPD) was extracted from the left ventricular free wall, and the mRNA levels of Kv1.4, 4.2, 4.3 and L type Ca2+ channel were determined by RNase protection assays [3].
  • The down-regulation of Kv4 family gene expression of Ito contributed to the pathophysiological changes in ventricular hypertrophy and pulmonary hypertension induced by MCT [4].

Psychiatry related information on Kcna4

  • 8. In contrast, larger diameter neurons associated with mechanoreception and proprioception express high levels of Kv1.1 and Kv1.2 without Kv1.4 or other Kv1 alpha subunits, suggesting that heteromers of these subunits predominate on large, myelinated afferent axons that extend from these cells [5].
  • This study indicates that the expression up-regulation of Kv1.4, Kv2.1, and Kv4.2 in Abeta-induced cognitive impairment might play an important role in the pathogenesis of Alzheimer's disease [6].

High impact information on Kcna4

  • We report here that heteromultimeric K+ channels composed of two different RCK proteins (RCK1 and RCK4) assemble after cotransfection of HeLa cells with the corresponding cDNAs and after coinjection of the corresponding cRNAs into Xenopus oocytes [7].
  • The heteromultimeric RCK1, 4 channel mediates a transient potassium outward current, similar to the RCK4 channel but inactivates more slowly, has a larger conductance and is more sensitive to block by dendrotoxin and tetraethylammonium chloride [7].
  • It is necessary for dendritic targeting of potassium channel Kv4.2 and is sufficient to target the axonally localized channels Kv1.3 and Kv1.4 to the dendrites [8].
  • Sigma receptors modulated voltage-gated K+ channels (Kv1.4 or Kv1.5) in different ways in the presence and absence of ligands [9].
  • To investigate mechanisms of localization, we used biolistic techniques to express GFP-tagged PSD-95 (PSD-95:GFP) and the K(+)-selective channel Kv1.4 in slices of rat cortex [10].

Biological context of Kcna4


Anatomical context of Kcna4


Associations of Kcna4 with chemical compounds

  • These results suggest that the fast recovery component of the tetraethylammonium-resistant I(A) in subfornical organ neurones depends upon Kv4, and that it can be modulated by angiotensin II [18].
  • Functional properties of a brain-specific NH2-terminally spliced modulator of Kv4 channels [19].
  • That T3 accelerated the developmental K+ channel isoform switch from Kv1.4 to Kv4.2 in vitro indicates the critical importance of thyroid hormone in postnatal K+ channel remodeling [20].
  • Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins [21].
  • Quantitative PCR analysis showed that stimulation with high concentration of KCl, BAY-K 8644, or 12-O-tetradecanoyl phorbol-13-acetate resulted in an immediate and substantial increase (two- to threefold) of Kv1.4 mRNA levels in spontaneously beating myocytes prepared from neonatal rat ventricles [22].

Physical interactions of Kcna4

  • Deleting the PSD-95 binding motif of Kv1.4 eliminated this recruitment, as did substituting a palmitoylation-deficient PSD-95 mutant [23].

Regulatory relationships of Kcna4

  • N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4 [24].
  • Kv1.4 inactivated over more depolarized voltages than Kv4.2 (V(1/2)inact = -49.3 +/- 1.4 mV, n = 12) [25].
  • The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased [22].

Other interactions of Kcna4

  • RT-PCR analysis revealed that rat uterus expressed all three Kv4 pore-forming subunits and KChIP2 and -4 auxiliary subunits [15].
  • These results suggest that diffusible factors coordinate the pregnancy-associated changes in molecular compositions of myometrial Kv4-KChIP channel complexes [15].
  • Here we investigated the role of N-glycosylation of Kv1.1 and Kv1.4 on their protein stability, cellular localization pattern, and trafficking to the cell surface [11].
  • There was an approximately twofold decrease in total Kv4 subfamily mRNA expression in atrial muscle relative to ventricular muscle and a 70% increase in total Kv1 subfamily mRNA [26].
  • The same mutation impaired the functional ability of PSD-95 to cluster Kv1.4 potassium channels in heterologous cells [27].

Analytical, diagnostic and therapeutic context of Kcna4

  • Here, we show that Ser229 found within the highly conserved T1 domain of Kv1.4 in cultured rat cortical neurones is phosphorylated by protein kinase A (PKA), as demonstrated by in vitro protein kinase assay and Western blotting with a polyclonal antibody specific against phosphorylated Ser229 [12].
  • Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs1-4 and Kv4 family alpha subunits in adult rat brain [28].
  • The distribution in the adult rat brain of the mRNA transcripts encoding the three known Kv4 subunits was studied by in situ hybridization histochemistry [29].
  • Membrane currents were measured with the use of the whole-cell arrangement of the patch clamp technique and the expression levels of the Kv1.4, Kv4.2 and Kv2.1 alpha subunits quantified using Western blot analysis [30].
  • The difference of mRNA expression of Kv1.4 was not significant in free wall of RV, left ventricle (LV), and septum in MCT group compared with control group [4].


  1. Decreased expression of Kv4.2 and novel Kv4.3 K+ channel subunit mRNAs in ventricles of renovascular hypertensive rats. Takimoto, K., Li, D., Hershman, K.M., Li, P., Jackson, E.K., Levitan, E.S. Circ. Res. (1997) [Pubmed]
  2. 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]
  3. Electrical remodeling of the ventricular myocardium in myocarditis: studies of rat experimental autoimmune myocarditis. Saito, J., Niwano, S., Niwano, H., Inomata, T., Yumoto, Y., Ikeda, K., Inuo, K., Kojima, J., Horie, M., Izumi, T. Circ. J. (2002) [Pubmed]
  4. Downregulation of Kv4.2 and Kv4.3 channel gene expression in right ventricular hypertrophy induced by monocrotaline in rat. Zhang, T.T., Cui, B., Dai, D.Z. Acta Pharmacol. Sin. (2004) [Pubmed]
  5. Distinct potassium channels on pain-sensing neurons. Rasband, M.N., Park, E.W., Vanderah, T.W., Lai, J., Porreca, F., Trimmer, J.S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. 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]
  7. Heteromultimeric channels formed by rat brain potassium-channel proteins. Ruppersberg, J.P., Schröter, K.H., Sakmann, B., Stocker, M., Sewing, S., Pongs, O. Nature (1990) [Pubmed]
  8. An evolutionarily conserved dileucine motif in Shal K+ channels mediates dendritic targeting. Rivera, J.F., Ahmad, S., Quick, M.W., Liman, E.R., Arnold, D.B. Nat. Neurosci. (2003) [Pubmed]
  9. The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Aydar, E., Palmer, C.P., Klyachko, V.A., Jackson, M.B. Neuron (2002) [Pubmed]
  10. Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel. Arnold, D.B., Clapham, D.E. Neuron (1999) [Pubmed]
  11. Glycosylation affects the protein stability and cell surface expression of Kv1.4 but Not Kv1.1 potassium channels. A pore region determinant dictates the effect of glycosylation on trafficking. Watanabe, I., Zhu, J., Recio-Pinto, E., Thornhill, W.B. J. Biol. Chem. (2004) [Pubmed]
  12. Neuronal transmission stimulates the phosphorylation of Kv1.4 channel at Ser229 through protein kinase A1. Tao, Y., Zeng, R., Shen, B., Jia, J., Wang, Y. J. Neurochem. (2005) [Pubmed]
  13. Altered K(+) channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4. Nishiyama, A., Ishii, D.N., Backx, P.H., Pulford, B.E., Birks, B.R., Tamkun, M.M. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  14. Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library. Tseng-Crank, J.C., Tseng, G.N., Schwartz, A., Tanouye, M.A. FEBS Lett. (1990) [Pubmed]
  15. Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy. Suzuki, T., Takimoto, K. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  16. Immunohistochemical co-expression of carbonic anhydrase II with Kv1.4 and TRPV1 in rat small-diameter trigeminal ganglion neurons. Tanimoto, T., Takeda, M., Nasu, M., Kadoi, J., Matsumoto, S. Brain Res. (2005) [Pubmed]
  17. Immunohistochemical localization of the voltage-gated potassium channel subunit Kv1.4 in the central nervous system of the adult rat. Luján, R., de Cabo de la Vega, C., Dominguez del Toro, E., Ballesta, J.J., Criado, M., Juiz, J.M. J. Chem. Neuroanat. (2003) [Pubmed]
  18. Transient outward K+ currents in rat dissociated subfornical organ neurones and angiotensin II effects. Ono, K., Toyono, T., Honda, E., Inenaga, K. J. Physiol. (Lond.) (2005) [Pubmed]
  19. Functional properties of a brain-specific NH2-terminally spliced modulator of Kv4 channels. Boland, L.M., Jiang, M., Lee, S.Y., Fahrenkrug, S.C., Harnett, M.T., O'Grady, S.M. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  20. Regulation of Kv4.2 and Kv1.4 K+ channel expression by myocardial hypertrophic factors in cultured newborn rat ventricular cells. Guo, W., Kamiya, K., Hojo, M., Kodama, I., Toyama, J. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  21. Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins. Holmqvist, M.H., Cao, J., Knoppers, M.H., Jurman, M.E., Distefano, P.S., Rhodes, K.J., Xie, Y., An, W.F. J. Neurosci. (2001) [Pubmed]
  22. Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy. Matsubara, H., Suzuki, J., Inada, M. J. Clin. Invest. (1993) [Pubmed]
  23. Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95. Wong, W., Schlichter, L.C. J. Biol. Chem. (2004) [Pubmed]
  24. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Topinka, J.R., Bredt, D.S. Neuron (1998) [Pubmed]
  25. Effect of Cd2+ on Kv4.2 and Kv1.4 expressed in Xenopus oocytes and on the transient outward currents in rat and rabbit ventricular myocytes. Wickenden, A.D., Tsushima, R.G., Losito, V.A., Kaprielian, R., Backx, P.H. Cell. Physiol. Biochem. (1999) [Pubmed]
  26. Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats. Dixon, J.E., McKinnon, D. Circ. Res. (1994) [Pubmed]
  27. Supramodular structure and synergistic target binding of the N-terminal tandem PDZ domains of PSD-95. Long, J.F., Tochio, H., Wang, P., Fan, J.S., Sala, C., Niethammer, M., Sheng, M., Zhang, M. J. Mol. Biol. (2003) [Pubmed]
  28. KChIPs and Kv4 alpha subunits as integral components of A-type potassium channels in mammalian brain. Rhodes, K.J., Carroll, K.I., Sung, M.A., Doliveira, L.C., Monaghan, M.M., Burke, S.L., Strassle, B.W., Buchwalder, L., Menegola, M., Cao, J., An, W.F., Trimmer, J.S. J. Neurosci. (2004) [Pubmed]
  29. Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain. Serôdio, P., Rudy, B. J. Neurophysiol. (1998) [Pubmed]
  30. 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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