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Kcna4  -  potassium voltage-gated channel, shaker...

Mus musculus

Synonyms: Kv1.4, Potassium voltage-gated channel subfamily A member 4, Voltage-gated potassium channel subunit Kv1.4
 
 
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Disease relevance of Kcna4

  • A premature pulse elicited ventricular tachycardia (VT) in Kv1.4(-/-) (n = 4/5) and Kv4.2DNxKv1.4(-/-) hearts (n = 5/5) but not Kv4.2DN hearts (n = 0/6) [1].
  • These features suggested that translation initiation in Kv1.4 might occur by the mechanism of internal ribosome entry, a mode of initiation employed by a variety of RNA viruses but only a limited number of vertebrate genes [2].
 

Psychiatry related information on Kcna4

 

High impact information on Kcna4

  • Immunoblotting confirmed the presence of Kv1.1, 1.2, 1.3, 1.5, 1.6, and 2.1, but not Kv1.4, in PASMCs [4].
  • It was recently reported that the slow transient outward K(+) current, I(to, s), that is evident in mouse left ventricular septal cells is eliminated in mice with a targeted deletion of the Kv1.4 gene (Kv1.4(-/-)) [5].
  • These observations demonstrate that upregulation of Kv1.4 contributes to the electrical remodeling evident in the ventricles of Kv4.2W362F-expressing mice and that elimination of both I(to,f) and I(to,s) has dramatic functional consequences [5].
  • Coexpression of Kv4.2W362F with Kv4.2 (or Kv4.3) attenuates the wild-type currents, and the effect is subfamily specific; ie, Kv4.2W362F does not affect heterologously expressed Kv1.4 currents [6].
  • Among K+ channel isoforms, Kv2.1, minK, and Kv1.4 were readily detected in tumors and at 1 day in culture [7].
 

Biological context of Kcna4

  • 2W362F-expressing left ventricular apex cells with properties indistinguishable from Ito,s in wild-type cells is accompanied by an increase in Kv1.4 protein expression, suggesting that the upregulation of Kv1.4 underlies the observed electrical remodeling in Kv4.2W362F-expressing transgenics [8].
  • 4. The mean best-fitting V (membrane potential at 50 % inactivation) values for myocytes from Kv1.4 +/+, Kv1.4+/- and Kv1 [9].
  • 5. The action of genistein on voltage-dependent K+ (Kv) currents was accompanied by a decrease in tyrosine phosphorylation of Kv1.4 as well as Kv1.5 and Kv2.1 encoding transient and slowly inactivating delayed-rectifier K+ channel alpha subunits, respectively [10].
  • To test this possibility we introduced the 5'-UTR of mouse Kv1.4 mRNA into the intercistronic region of a bicistronic vector containing two tandem reporter genes, chloramphenicol acetyltransferase and luciferase [2].
 

Anatomical context of Kcna4

  • We also show that the upstream approximately 1.0 kb and the downstream approximately 0.2 kb of the Kv1.4 5'-NCR independently mediated internal ribosome entry; however, separately, these sequences were less efficient in mediating internal ribosome entry than when together in the complete (and contiguous) 5'-NCR [11].
  • 7. Thus, Kv1.4 is not the molecular basis of Ito in adult murine ventricular myocytes [9].
  • To determine the effects of voltage-gated K+ channel expression on processes not associated with electrically excitable cells, we studied cell volume, membrane potential, Na(+)-K(+)-ATPase activity, and alanine transport after the stable expression of the Kv1.4 and Kv1.5 human K+ channels in Ltk- mouse fibroblasts (L-cells) [12].
 

Associations of Kcna4 with chemical compounds

  • 5. Nearly the entire inactivating component as well as more than 60 % of the steady-state outward current was eliminated by 1 mM 4-aminopyridine in Kv1.4+/+, Kv1.4+/- and Kv1.4-/- myocytes [9].
  • In the absence of K+o, current through Kv1.4 was almost completely abolished due to the presence of a charged lysine residue at position 533 at the entrance to the pore [13].
  • Flecainide (10 microM) had minimal effects on Kv1.4 currents, but reduced Kv4.2 peak current by 53% and increased the apparent rate of inactivation consistent with open channel block [14].
  • In L-cells, 10 to 100 microM OPC-18790 reduced Kv1.4, Kv1.5 and Kv2.1 currents by <30%, whereas quinidine was a more potent blocker (EC50 < 10 microM) and the I(Kr)-specific blocker dofetilide was without effect [15].
  • Expression of the Kv1.4 channel did not alter alanine transport relative to wild-type or sham-transfected cells [12].
 

Regulatory relationships of Kcna4

  • In addition, the slow transient outward K+ current, I(to,s), and the Kv1.4 protein (which encodes I(to,s)) are upregulated in Kv4.2(-/-) ventricles [16].
 

Other interactions of Kcna4

  • Immunoblot and immunohistochemical studies confirmed the existence of Kv1.4 and Kv4.2/3 subunits [17].
  • 4. 3. Neither the 4-AP-sensitive, slowly inactivating K+ current, IK,slow, nor the steady-state non-inactivating K+ current, ISS, is affected in Kv1.4-/- mouse left ventricular cells [8].
 

Analytical, diagnostic and therapeutic context of Kcna4

References

  1. Dispersion of repolarization and refractoriness are determinants of arrhythmia phenotype in transgenic mice with long QT. London, B., Baker, L.C., Petkova-Kirova, P., Nerbonne, J.M., Choi, B.R., Salama, G. J. Physiol. (Lond.) (2007) [Pubmed]
  2. Translation initiation of a cardiac voltage-gated potassium channel by internal ribosome entry. Negulescu, D., Leong, L.E., Chandy, K.G., Semler, B.L., Gutman, G.A. J. Biol. Chem. (1998) [Pubmed]
  3. Differential effects of acute and chronic electroconvulsive shock on the abundance of messenger RNAs for voltage-dependent potassium channel subunits in the rat brain. Pei, Q., Burnet, P.W., Grahame-Smith, D.G., Zetterström, T.S. Neuroscience (1997) [Pubmed]
  4. 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]
  5. Functional consequences of elimination of i(to,f) and i(to,s): early afterdepolarizations, atrioventricular block, and ventricular arrhythmias in mice lacking Kv1.4 and expressing a dominant-negative Kv4 alpha subunit. Guo, W., Li, H., London, B., Nerbonne, J.M. Circ. Res. (2000) [Pubmed]
  6. 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]
  7. K+ currents and K+ channel mRNA in cultured atrial cardiac myocytes (AT-1 cells). Yang, T., Wathen, M.S., Felipe, A., Tamkun, M.M., Snyders, D.J., Roden, D.M. Circ. Res. (1994) [Pubmed]
  8. Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes. Guo, W., Xu, H., London, B., Nerbonne, J.M. J. Physiol. (Lond.) (1999) [Pubmed]
  9. The transient outward current in mice lacking the potassium channel gene Kv1.4. London, B., Wang, D.W., Hill, J.A., Bennett, P.B. J. Physiol. (Lond.) (1998) [Pubmed]
  10. Tyrosine kinases modulate K+ channel gating in mouse Schwann cells. Peretz, A., Sobko, A., Attali, B. J. Physiol. (Lond.) (1999) [Pubmed]
  11. Structurally distinct elements mediate internal ribosome entry within the 5'-noncoding region of a voltage-gated potassium channel mRNA. Jang, G.M., Leong, L.E., Hoang, L.T., Wang, P.H., Gutman, G.A., Semler, B.L. J. Biol. Chem. (2004) [Pubmed]
  12. 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]
  13. Regulation of mammalian Shaker-related K+ channels: evidence for non-conducting closed and non-conducting inactivated states. Jäger, H., Rauer, H., Nguyen, A.N., Aiyar, J., Chandy, K.G., Grissmer, S. J. Physiol. (Lond.) (1998) [Pubmed]
  14. Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current. Yeola, S.W., Snyders, D.J. Cardiovasc. Res. (1997) [Pubmed]
  15. Inhibition of cardiac potassium currents by the vesnarinone analog OPC-18790: comparison with quinidine and dofetilide. Yang, T., Snyders, D.J., Roden, D.M. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  16. Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and molecular remodeling, with no evidence of ventricular hypertrophy or myocardial dysfunction. Guo, W., Jung, W.E., Marionneau, C., Aimond, F., Xu, H., Yamada, K.A., Schwarz, T.L., Demolombe, S., Nerbonne, J.M. Circ. Res. (2005) [Pubmed]
  17. Pituitary adenylate cyclase activating polypeptide reduces expression of Kv1.4 and Kv4.2 subunits underlying A-type K(+) current in adult mouse olfactory neuroepithelia. Han, P., Lucero, M.T. Neuroscience (2006) [Pubmed]
 
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