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Gene Review

KCNA5  -  potassium channel, voltage gated shaker...

Homo sapiens

Synonyms: ATFB7, HCK1, HK2, HPCN1, KV1.5, ...
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Disease relevance of KCNA5

  • A long-range restriction map of an 800-kb region was constructed and used to refine the mesothelioma breakpoint to a region of approximately 100 kb, flanked by the potassium channel genes KCNA1 and KCNA5 [1].
  • We have shown that acute hypoxia selectively inhibits I(K(V)) through KCNA5 channels in PASMC [2].
  • Induction of apoptosis in PASMC by KCNA5 gene transfer may serve as an important strategy for preventing the progression of pulmonary vascular wall thickening and for treating patients with idiopathic pulmonary arterial hypertension (IPAH) [3].
  • Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation [4].
  • Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients [5].

High impact information on KCNA5

  • A delayed rectifier K+ channel such as hPCN1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion [6].
  • Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA revealed a voltage-dependent outward K+ current that inactivated slowly with time [6].
  • From 70 CEPH parents screened with a StyI RFLP for hPCN1, four informative families were found each with both parental and maternal grandparents and 6-11 children per family [7].
  • Dinucleotide repeat polymorphism at the KCNA5 locus [8].
  • In the present study, we have analyzed this region in the human renal proximal tubular epithelial cell line HK-2 [9].

Biological context of KCNA5

  • Molecular biological characterization of the YAC-insert DNAs revealed that three KCNA genes--KCNA1, KCNA5, KCNA6--are clustered within approximately 300 kb of insert-DNA derived from chromosome 12p13 [10].
  • Overexpression of human KCNA5 increases IK V and enhances apoptosis [3].
  • KCNA5 is a Kv channel alpha-subunit that forms functional Kv channels in PASMC and regulates resting membrane potential [2].
  • Transient transfection of KCNA5 caused 25- to 34-fold increase in KCNA5 channel protein level and 24- to 29-fold increase in Kv channel current (I(K(V))) at +60 mV in COS-7 and rat PASMC, respectively [3].
  • In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia [5].

Anatomical context of KCNA5


Associations of KCNA5 with chemical compounds

  • Furthermore, ST-induced apoptotic cell shrinkage was significantly accelerated in COS-7 cells and rat PASMC transfected with KCNA5, and blockade of KCNA5 channels with 4-aminopyridine (4-AP) reduced K+ currents through KCNA5 channels and inhibited ST-induced apoptosis in KCNA5-transfected COS-7 cells [3].
  • Both enzymes also catalyzed 6 beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione, although hPCN1 exhibited several-fold higher expressed activity than hPCN3 [11].
  • Clear differences were also detected in their catalytic activities toward the immunosuppressive drug cyclosporine, with two hydroxylated metabolites (M1 and M17) and one demethylated metabolite (M21) formed by hPCN1 but only one metabolite (M1) formed by hPCN3 [11].
  • These data indicate that 1) the charged form of quinidine blocks the HK2 channel after it opens, 2) binding occurs within the transmembrane electrical field (probably in or near the ion permeation pathway), and 3) unbinding is required before the channel can close [12].
  • The effect of clofilium on potassium conductance was studied in excised membrane patches from Chinese hamster ovary cells stably transfected with the Kv1.5/hPCN1 delayed rectifier K+ channel gene [14].

Regulatory relationships of KCNA5


Other interactions of KCNA5

  • Gene expression studies of Shaker KV1 transcripts have shown that of the dominant species present in arterial SMCs, KV1.2 expression is higher, whereas KV1.5 is the same in SMCs from hypertensive compared to normal animals [15].
  • The library was screened with an hPCN1 cDNA probe resulting in the isolation of a unique full-length cDNA that was sequenced and shown to encode hPCN3 [11].
  • Three natural allelic cDNAs coding for P-450 3A4, the major form in human liver, namely NF25, NF10 and hPCN1, have been expressed in Saccharomyces cerevisiae [13].
  • We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months [16].

Analytical, diagnostic and therapeutic context of KCNA5


  1. A physical map of the region spanning the chromosome 12 translocation breakpoint in a mesothelioma with a t(X;12)(q22;p13). Aerssens, J., Guo, C., Vermeesch, J., Baens, M., Browne, D., Litt, M., Van Den Berghe, H., Marynen, P. Cytogenet. Cell Genet. (1995) [Pubmed]
  2. Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. Platoshyn, O., Brevnova, E.E., Burg, E.D., Yu, Y., Remillard, C.V., Yuan, J.X. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  3. Overexpression of human KCNA5 increases IK V and enhances apoptosis. Brevnova, E.E., Platoshyn, O., Zhang, S., Yuan, J.X. Am. J. Physiol., Cell Physiol. (2004) [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. Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients. Nielsen, N.H., Winkel, B.G., Kanters, J.K., Schmitt, N., Hofman-Bang, J., Jensen, H.S., Bentzen, B.H., Sigurd, B., Larsen, L.A., Andersen, P.S., Haunsø, S., Kjeldsen, K., Grunnet, M., Christiansen, M., Olesen, S.P. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  6. Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Philipson, L.H., Hice, R.E., Schaefer, K., LaMendola, J., Bell, G.I., Nelson, D.J., Steiner, D.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  7. The gene CYP3 encoding P450pcn1 (nifedipine oxidase) is tightly linked to the gene COL1A2 encoding collagen type 1 alpha on 7q21-q22.1. Brooks, B.A., McBride, O.W., Dolphin, C.T., Farrall, M., Scambler, P.J., Gonzalez, F.J., Idle, J.R. Am. J. Hum. Genet. (1988) [Pubmed]
  8. Dinucleotide repeat polymorphism at the KCNA5 locus. Phromchotikul, T., Browne, D.L., Curran, M.E., Keating, M.T., Litt, M. Hum. Mol. Genet. (1993) [Pubmed]
  9. Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2 gene. Monslow, J., Williams, J.D., Fraser, D.J., Michael, D.R., Foka, P., Kift-Morgan, A.P., Luo, D.D., Fielding, C.A., Craig, K.J., Topley, N., Jones, S.A., Ramji, D.P., Bowen, T. J. Biol. Chem. (2006) [Pubmed]
  10. Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Albrecht, B., Weber, K., Pongs, O. Recept. Channels (1995) [Pubmed]
  11. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. Aoyama, T., Yamano, S., Waxman, D.J., Lapenson, D.P., Meyer, U.A., Fischer, V., Tyndale, R., Inaba, T., Kalow, W., Gelboin, H.V. J. Biol. Chem. (1989) [Pubmed]
  12. Time-, voltage-, and state-dependent block by quinidine of a cloned human cardiac potassium channel. Snyders, J., Knoth, K.M., Roberds, S.L., Tamkun, M.M. Mol. Pharmacol. (1992) [Pubmed]
  13. Expression in yeast of three allelic cDNAs coding for human liver P-450 3A4. Different stabilities, binding properties and catalytic activities of the yeast-produced enzymes. Peyronneau, M.A., Renaud, J.P., Jaouen, M., Urban, P., Cullin, C., Pompon, D., Mansuy, D. Eur. J. Biochem. (1993) [Pubmed]
  14. Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel. Malayev, A.A., Nelson, D.J., Philipson, L.H. Mol. Pharmacol. (1995) [Pubmed]
  15. Changes in the expression and function of arterial potassium channels during hypertension. Cox, R.H. Vascul. Pharmacol. (2002) [Pubmed]
  16. Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation. Lai, L.P., Su, M.J., Lin, J.L., Lin, F.Y., Tsai, C.H., Chen, Y.S., Tseng, Y.Z., Lien, W.P., Huang, S.K. Cardiology (1999) [Pubmed]
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