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Gene Review

Kcna5  -  potassium channel, voltage gated shaker...

Rattus norvegicus

Synonyms: Kv1, Kv1.5, Potassium voltage-gated channel subfamily A member 5, RCK7, RK4, ...
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Disease relevance of Kcna5

  • Exposure to chronic hypoxia decreased mRNA and protein levels of Kv1.1, Kv1.5, Kv1.6, Kv2.1, and Kv4.3 alpha-subunits in dPAs but did not alter gene or protein expression of these channels in aorta [1].
  • Regardless of the etiology of the hypertrophy, the amounts of Kv1.4 and Kv1.5 mRNAwere similar in treated, sham and control rats [2].
  • In particular, increased Kv1.5 gene expression, having a transient nature, implied the possible biochemical electrical remodeling unique to paroxysmal tachycardia [3].
  • 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) [4].
  • RESULTS: MMI treatment induced hypothyroidism and resulted in a significant decrease in the mRNA levels of Kv1.5, Kv2.1 and Kv4.2 (19%, 77% and 61% of control value, respectively; n = 6, p < 0.05) [4].

Psychiatry related information on Kcna5

  • 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].
  • Our results suggest that Kv1.5 and Kv1.6 Shaker K+ channels play an important role in regulating motor activity that increases in mRNA and protein levels of the spinal cord K+ channels after chronic morphine exposure could be viewed as a cellular adaptation which compensates for a persistent opioid-induced inhibition of K+ channel activity [6].

High impact information on Kcna5


Chemical compound and disease context of Kcna5


Biological context of Kcna5

  • A cAMP response element (CRE) consensus signal was identified in the 5'-noncoding region. cAMP regulates the expression of Kv1.5 gene in a cell-specific manner [14].
  • Transient transfection assays using 5'-deletion mutations of Kv1.5 5'-flanking sequences revealed that the CRE located at +636 can confer the cAMP inducibility to Kv1.5 reporter gene constructs and binds to CRE-binding protein (CREB) and CRE modulator protein (CREM) in electromobility gel shift assays [14].
  • 5. By further exploring the structure-activity relationship around Psora-4 through a combination of traditional medicinal chemistry and whole-cell patch-clamp, we identified a series of new phenoxyalkoxypsoralens that exhibit 2- to 50-fold selectivity for Kv1.3 over Kv1.5, depending on their exact substitution pattern [15].
  • Transient transfection experiments in COS-7 cells revealed that SAP97 and Kv1.5 polypeptides formed perinuclear clustered complexes that could be coimmunoprecipitated [16].
  • Electrophysiological findings that the shortening of the action potential produced by 4-hour pacing was almost abolished by a low concentration of 4-aminopyridine implied that the increased Kv1.5 protein was functioning [3].

Anatomical context of Kcna5


Associations of Kcna5 with chemical compounds

  • Heterologously expressed human PASMC Kv1.5 generated an O2- and correolide-sensitive I(K) like that in resistance PASMCs [19].
  • These increased currents were blocked by 1 mmol/L 4-aminopyridine, and the specific Kv1.5 antagonist, DMM (100 nM) [18].
  • Injection of dexamethasone into adrenalectomized rats acted within a day to increase ventricular Kv1.5 mRNA and immunoreactive protein approximately 50-fold and approximately 20-fold, respectively [20].
  • Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40% [21].
  • Furthermore, cardiac myocytes cocultured with cells that endogenously (Mv 1 Lu) or heterologously (Chinese hamster ovary cells) express the receptor-type protein tyrosine phosphatase mu (RPTPmu) display Kv1.5 mRNA levels paralleling that which was observed in myocytes cultured under high-density conditions and in intact tissue [22].

Physical interactions of Kcna5


Regulatory relationships of Kcna5

  • Kv beta 1.1 induced inactivation in members of the Kv1 subfamily with the exception of Kv 1.6; no inactivation of Kv 2.1, Kv 3.4 delta 2-28 and Kv4.1 channels could be observed [24].
  • The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased [25].
  • In contrast to PE, a 48% enhancement of the protein expression of Kv1.5 channel was induced by IGF-1 and this stimulation was specifically blocked by genistein [26].

Other interactions of Kcna5

  • The Kv2 mRNA is expressed only in brain, whereas the Kv1 and Kv3 transcripts are found in several other tissues as well [27].
  • 1. Anti-Kv1.5 and anti-Kv2.1 caused additive depolarization in resistance PASMCs (Kv1.5>Kv2.1) and inhibited hypoxic depolarization [19].
  • 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 [28].
  • The increase of Kv1.5 and the decrease of Kv4.2 and Kv4.3 mRNA levels were both rate dependent [3].
  • The chimaeric beta-subunits (beta 1/ beta 2 and beta 3/ beta 2) induced fast inactivation of several Kv1 channels, indicating that Kv beta 2 associates with these alpha-subunits [24].

Analytical, diagnostic and therapeutic context of Kcna5


  1. Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery. Wang, J., Weigand, L., Wang, W., Sylvester, J.T., Shimoda, L.A. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [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. Short-term effects of rapid pacing on mRNA level of voltage-dependent K(+) channels in rat atrium: electrical remodeling in paroxysmal atrial tachycardia. Yamashita, T., Murakawa, Y., Hayami, N., Fukui, E., Kasaoka, Y., Inoue, M., Omata, M. Circulation (2000) [Pubmed]
  4. 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]
  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. Chronic morphine administration enhances the expression of Kv1.5 and Kv1.6 voltage-gated K+ channels in rat spinal cord. Matus-Leibovitch, N., Vogel, Z., Ezra-Macabee, V., Etkin, S., Nevo, I., Attali, B. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  7. 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]
  8. Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue. Mays, D.J., Foose, J.M., Philipson, L.H., Tamkun, M.M. J. Clin. Invest. (1995) [Pubmed]
  9. Glucocorticoid induced up-regulation of a pituitary K+ channel mRNA in vitro and in vivo. Attardi, B., Takimoto, K., Gealy, R., Severns, C., Levitan, E.S. Recept. Channels (1993) [Pubmed]
  10. A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum. Akhtar, S., McIntosh, P., Bryan-Sisneros, A., Barratt, L., Robertson, B., Dolly, J.O. Biochemistry (1999) [Pubmed]
  11. Regulation of cardiac Kv1.5 K+ channel expression by cardiac fibroblasts and mechanical load in cultured newborn rat ventricular myocytes. Guo, W., Kamiya, K., Kada, K., Kodama, I., Toyama, J. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  12. Effects of thyroid and glucocorticoid hormones on Kv1.5 potassium channel gene expression in the rat left ventricle. Nishiyama, A., Kambe, F., Kamiya, K., Yamaguchi, S., Murata, Y., Seo, H., Toyama, J. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  13. In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Pozeg, Z.I., Michelakis, E.D., McMurtry, M.S., Thébaud, B., Wu, X.C., Dyck, J.R., Hashimoto, K., Wang, S., Moudgil, R., Harry, G., Sultanian, R., Koshal, A., Archer, S.L. Circulation (2003) [Pubmed]
  14. The transcription of a mammalian voltage-gated potassium channel is regulated by cAMP in a cell-specific manner. Mori, Y., Matsubara, H., Folco, E., Siegel, A., Koren, G. J. Biol. Chem. (1993) [Pubmed]
  15. Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Schmitz, A., Sankaranarayanan, A., Azam, P., Schmidt-Lassen, K., Homerick, D., Hänsel, W., Wulff, H. Mol. Pharmacol. (2005) [Pubmed]
  16. SAP97 interacts with Kv1.5 in heterologous expression systems. Murata, M., Buckett, P.D., Zhou, J., Brunner, M., Folco, E., Koren, G. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  17. Kv2 channels oppose myogenic constriction of rat cerebral arteries. Amberg, G.C., Santana, L.F. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  18. Kv1.5 surface expression is modulated by retrograde trafficking of newly endocytosed channels by the dynein motor. Choi, W.S., Khurana, A., Mathur, R., Viswanathan, V., Steele, D.F., Fedida, D. Circ. Res. (2005) [Pubmed]
  19. 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]
  20. Glucocorticoid induction of Kv1.5 K+ channel gene expression in ventricle of rat heart. Takimoto, K., Levitan, E.S. Circ. Res. (1994) [Pubmed]
  21. 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]
  22. RPTPmu and protein tyrosine phosphorylation regulate K(+) channel mRNA expression in adult cardiac myocytes. Hershman, K.M., Levitan, E.S. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  23. 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]
  24. Functional characterization of Kv channel beta-subunits from rat brain. Heinemann, S.H., Rettig, J., Graack, H.R., Pongs, O. J. Physiol. (Lond.) (1996) [Pubmed]
  25. 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]
  26. alpha1-adrenoceptor agonists and IGF-1, myocardial hypertrophic factors, regulate the Kv1.5 K+ channel expression differentially in cultured newborn rat ventricular cells. Guo, W., Kamiya, K., Yasui, K., Kodama, I., Toyama, J. Pflugers Arch. (1998) [Pubmed]
  27. Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Swanson, R., Marshall, J., Smith, J.S., Williams, J.B., Boyle, M.B., Folander, K., Luneau, C.J., Antanavage, J., Oliva, C., Buhrow, S.A. Neuron (1990) [Pubmed]
  28. Quantitative analysis of potassium channel mRNA expression in atrial and ventricular muscle of rats. Dixon, J.E., McKinnon, D. Circ. Res. (1994) [Pubmed]
  29. 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]
  30. Surface Charges of K channels. Effects of strontium on five cloned channels expressed in Xenopus oocytes. Elinder, F., Madeja, M., Arhem, P. J. Gen. Physiol. (1996) [Pubmed]
  31. Modulation of Kv1.5 currents by Src tyrosine phosphorylation: potential role in the differentiation of astrocytes. MacFarlane, S.N., Sontheimer, H. J. Neurosci. (2000) [Pubmed]
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