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Gene Review

Kcna5  -  potassium voltage-gated channel, shaker...

Mus musculus

Synonyms: KV1-5, Kv1.5, Potassium voltage-gated channel subfamily A member 5, Voltage-gated potassium channel subunit Kv1.5
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Disease relevance of Kcna5


High impact information on Kcna5

  • Permeation selectivity was studied in two human potassium channels, Kv2.1 and Kv1.5, expressed in a mouse cell line [6].
  • Both Kv2.1 and Kv1.5 contribute to the initiation of HPV [7].
  • This occurs together with increased activity of delayed- rectifier, voltage-gated potassium (Kv) channels and with hyperphosphorylation of Kv1.5 and Kv2.1 Kv channel alpha-subunits in sciatic nerve tissue and in primary Schwann cells [8].
  • The Kv1.5 and Kv2.1 K+-channel alpha subunits are constitutively tyrosine phosphorylated and physically associate with Fyn both in cultured SCs and in the sciatic nerve in vivo [9].
  • The present work shows that arachidonic acid and some other long chain polyunsaturated fatty acids such as docosahexaenoic acid, which is abundant in fish oil, produce a direct open channel block of the major voltage-dependent K+ channel (Kv1.5) cloned in cardiac cells [10].

Biological context of Kcna5


Anatomical context of Kcna5


Associations of Kcna5 with chemical compounds

  • Both depletion of cellular cholesterol and inhibition of sphingolipid synthesis alter Kv1.5 channel function by inducing a hyperpolarizing shift in the voltage dependence of activation and inactivation [15].
  • Gal(beta1-3)GalNAc binding sites did not have an obligatory co-localization with voltage-gated sodium channels or the potassium ion channels Kv1.1 and Kv1.5 and are thus not likely carried by these ion channels [18].
  • Long-term restitution of 4-aminopyridine-sensitive currents in Kv1DN ventricular myocytes using adeno-associated virus-mediated delivery of Kv1.5 [3].
  • In these experiments, point mutations were introduced in the pore region of Kv1.5 to change the tryptophan (W) at position 461 to phenylalanine (F) to produce a nonconducting subunit, Kv1.5W461F, that is shown to function as a Kv1 subfamily-specific dominant negative (Kv1.5DN) [19].
  • These results indicate that delayed rectifier channels such as Kv1.5 can play a key role in the control of cell membrane potential, cell volume, Na(+)-K(+)-ATPase activity, and electrogenic alanine transport across the plasma membrane of electrically unexcitable cells [17].

Regulatory relationships of Kcna5

  • When Kv1.1 was expressed as a heterotetrameric complex with Kv1.5, block by DTX-K dominated, indicating that one or more subunits of Kv1.1 rendered the heterotetrameric channel sensitive to DTX-K [20].
  • 1. Peak outward K+ current densities are attenuated significantly in atrial myocytes isolated from P15 and adult Kv2.1N216Flag-expressing animals and in P15 cells exposed to AsODNs targeted against either Kv1.5 or Kv2 [21].

Other interactions of Kcna5

  • We characterized heteromultimeric channel complexes that consist of either Kv1.5 and Kv1.2 or Kv1.5 and Kv1 [22].
  • 4. RNase protection analysis comparing the steady-state levels of native Kv1.5 and Kv1.1N206Tag transcripts revealed an excess of Kv1.1N206Tag transcript [1].
  • Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel [23].
  • Androgen replacement in male C57BL/6 mice as well as in castrated male CD-1 mice shortened ventricular repolarization, increased I(Kur) current density, and increased expression of Kv1.5 channels [24].
  • Except for KCNE1, Northern blots (KCNQ1, MERG, Kv1.5, connexins 40 and 43, TREK1, and TASK1) did not detect sex differences [25].

Analytical, diagnostic and therapeutic context of Kcna5


  1. A cellular model for long QT syndrome. Trapping of heteromultimeric complexes consisting of truncated Kv1.1 potassium channel polypeptides and native Kv1.4 and Kv1.5 channels in the endoplasmic reticulum. Folco, E., Mathur, R., Mori, Y., Buckett, P., Koren, G. J. Biol. Chem. (1997) [Pubmed]
  2. Oxygen sensitivity of cloned voltage-gated K(+) channels expressed in the pulmonary vasculature. Hulme, J.T., Coppock, E.A., Felipe, A., Martens, J.R., Tamkun, M.M. Circ. Res. (1999) [Pubmed]
  3. Long-term restitution of 4-aminopyridine-sensitive currents in Kv1DN ventricular myocytes using adeno-associated virus-mediated delivery of Kv1.5. Kodirov, S.A., Brunner, M., Busconi, L., Koren, G. FEBS Lett. (2003) [Pubmed]
  4. Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Olson, T.M., Alekseev, A.E., Liu, X.K., Park, S., Zingman, L.V., Bienengraeber, M., Sattiraju, S., Ballew, J.D., Jahangir, A., Terzic, A. Hum. Mol. Genet. (2006) [Pubmed]
  5. Electrical remodeling and arrhythmias in long-QT syndrome: lessons from genetic models in mice. Koren, G. Ann. Med. (2004) [Pubmed]
  6. Permeation selectivity by competition in a delayed rectifier potassium channel. Korn, S.J., Ikeda, S.R. Science (1995) [Pubmed]
  7. Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. Archer, S.L., Souil, E., Dinh-Xuan, A.T., Schremmer, B., Mercier, J.C., El Yaagoubi, A., Nguyen-Huu, L., Reeve, H.L., Hampl, V. J. Clin. Invest. (1998) [Pubmed]
  8. Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon. Peretz, A., Gil-Henn, H., Sobko, A., Shinder, V., Attali, B., Elson, A. EMBO J. (2000) [Pubmed]
  9. Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. Sobko, A., Peretz, A., Attali, B. EMBO J. (1998) [Pubmed]
  10. External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids. Honoré, E., Barhanin, J., Attali, B., Lesage, F., Lazdunski, M. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  11. Molecular genetic analysis of distal mouse chromosome 6 defines gene order and positions of the deafwaddler and opisthotonos mutations. Street, V.A., Robinson, L.C., Erford, S.K., Tempel, B.L. Genomics (1995) [Pubmed]
  12. KChIP2 modulates the cell surface expression of Kv 1.5-encoded K(+) channels. Li, H., Guo, W., Mellor, R.L., Nerbonne, J.M. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  13. Tyrosine kinases modulate K+ channel gating in mouse Schwann cells. Peretz, A., Sobko, A., Attali, B. J. Physiol. (Lond.) (1999) [Pubmed]
  14. Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta 2.1 subunits. Uebele, V.N., England, S.K., Chaudhary, A., Tamkun, M.M., Snyders, D.J. J. Biol. Chem. (1996) [Pubmed]
  15. Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. Martens, J.R., Sakamoto, N., Sullivan, S.A., Grobaski, T.D., Tamkun, M.M. J. Biol. Chem. (2001) [Pubmed]
  16. The effects of putative K+ channel blockers on volume regulation of murine spermatozoa. Barfield, J.P., Yeung, C.H., Cooper, T.G. Biol. Reprod. (2005) [Pubmed]
  17. Influence of cloned voltage-gated K+ channel expression on alanine transport, Rb+ uptake, and cell volume. Felipe, A., Snyders, D.J., Deal, K.K., Tamkun, M.M. Am. J. Physiol. (1993) [Pubmed]
  18. The distribution of ganglioside-like moieties in peripheral nerves. Sheikh, K.A., Deerinck, T.J., Ellisman, M.H., Griffin, J.W. Brain (1999) [Pubmed]
  19. Selective elimination of I(K,slow1) in mouse ventricular myocytes expressing a dominant negative Kv1.5alpha subunit. Li, H., Guo, W., Yamada, K.A., Nerbonne, J.M. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  20. Functional and molecular expression of a voltage-dependent K(+) channel (Kv1.1) in interstitial cells of Cajal. Hatton, W.J., Mason, H.S., Carl, A., Doherty, P., Latten, M.J., Kenyon, J.L., Sanders, K.M., Horowitz, B. J. Physiol. (Lond.) (2001) [Pubmed]
  21. Molecular diversity of the repolarizing voltage-gated K+ currents in mouse atrial cells. Bou-Abboud, E., Li, H., Nerbonne, J.M. J. Physiol. (Lond.) (2000) [Pubmed]
  22. Heteromultimeric delayed-rectifier K+ channels in schwann cells: developmental expression and role in cell proliferation. Sobko, A., Peretz, A., Shirihai, O., Etkin, S., Cherepanova, V., Dagan, D., Attali, B. J. Neurosci. (1998) [Pubmed]
  23. Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. Leicher, T., Bähring, R., Isbrandt, D., Pongs, O. J. Biol. Chem. (1998) [Pubmed]
  24. Sex and strain differences in adult mouse cardiac repolarization: importance of androgens. Brouillette, J., Rivard, K., Lizotte, E., Fiset, C. Cardiovasc. Res. (2005) [Pubmed]
  25. Mice display sex differences in halothane-induced polymorphic ventricular tachycardia. Drici, M.D., Baker, L., Plan, P., Barhanin, J., Romey, G., Salama, G. Circulation (2002) [Pubmed]
  26. Targeted replacement of KV1.5 in the mouse leads to loss of the 4-aminopyridine-sensitive component of I(K,slow) and resistance to drug-induced qt prolongation. London, B., Guo, W., Pan Xh, n.u.l.l., Lee, J.S., Shusterman, V., Rocco, C.J., Logothetis, D.A., Nerbonne, J.M., Hill, J.A. Circ. Res. (2001) [Pubmed]
  27. Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca(2+) channels. Thorne, G.D., Conforti, L., Paul, R.J. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  28. Identification, cloning and expression of rabbit vascular smooth muscle Kv1.5 and comparison with native delayed rectifier K+ current. Clément-Chomienne, O., Ishii, K., Walsh, M.P., Cole, W.C. J. Physiol. (Lond.) (1999) [Pubmed]
  29. Single channel analysis reveals different modes of Kv1.5 gating behavior regulated by changes of external pH. Kwan, D.C., Fedida, D., Kehl, S.J. Biophys. J. (2006) [Pubmed]
  30. Presence of the Kv1.5 K(+) channel in the sinoatrial node. Dobrzynski, H., Rothery, S.M., Marples, D.D., Coppen, S.R., Takagishi, Y., Honjo, H., Tamkun, M.M., Henderson, Z., Kodama, I., Severs, N.J., Boyett, M.R. J. Histochem. Cytochem. (2000) [Pubmed]
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