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Kv1.5

Family: Voltage-gated potassium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Gene Expression and Pathophysiology
References
Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 613 12p13.3 KCNA5 potassium voltage-gated channel, shaker-related subfamily, member 5 1,5,24
Mouse 6 1 602 6 F3 Kcna5 potassium voltage-gated channel, shaker-related subfamily, member 5
Rat 6 1 602 4q42-44 Kcna5 potassium voltage-gated channel, shaker-related subfamily, member 5
Previous and Unofficial Names
HpCN1
HK2
HCK1
KV1
fHK
RK3
RMK2
HuK (II)
Kv1.5
Potassium (K+) channel protein alpha 5
RCK7
RK4
potassium voltage gated channel shaker related subfamily member 5
potassium voltage gated channel, shaker related subfamily, member 5
potassium voltage-gated channel subfamily A member 5
potassium voltage-gated channel, shaker-related subfamily, member 5
voltage-gated potassium channel subunit Kv1.5
Database Links
ChEMBL Target 10198 (Hs), 100469 (Mm)
Ensembl ENSG00000130037 (Hs), ENSMUSG00000045534 (Mm), ENSRNOG00000019719 (Rn)
Entrez Gene 3741 (Hs), 16493 (Mm), 25470 (Rn)
GeneCards KCNA5 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcna5 (Mm)
HomoloGene 1683 (Hs)
Human Protein Reference Database 08888 (Hs)
InterPro P22460 (Hs), Q61762 (Mm), P19024 (Rn)
KEGG Gene hsa:3741 (Hs), mmu:16493 (Mm), rno:25470 (Rn)
OMIM 176267 (Hs)
Orphanet Gene ORPHA168086 (Hs)
PharmGKB Gene PA208 (Hs)
PhosphoSitePlus P22460 (Hs), Q61762 (Mm)
Protein Ontology (PRO) PRO:000000812 (Hs)
RefSeq Nucleotide NM_002234 (Hs), NM_145983 (Mm), NM_012972 (Rn)
RefSeq Protein NP_002225 (Hs), NP_666095 (Mm), NP_037104 (Rn)
TreeFam ENSG00000130037 (Hs), ENSMUSG00000045534 (Mm), ENSRNOG00000019719 (Rn)
UniGene Hs. 150208 (Hs)
UniProt P22460 (Hs), Q61762 (Mm), P19024 (Rn)
Wikipedia Kv1.5
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated potassium channels Kv1.5 Search by accession number: Q61762, P19024, P22460
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kvβ2 10,36,40
Kvβ1 10,28,40
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
SAP97 22
Src Tyrosine Kinase 11,31
KCNA3B 15
α-actinin 2 (fyn) 18
KChaP (caveolin) 17,41
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [8.0 pS]
References:  8
Species:  Human
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  8
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -14.0 - 29 Mouse LTK cell line Mouse
Inactivation  -10.0 260.0 – 5000.0 29
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -14.0 23.0 8 MEL Human
Inactivation  - - 8
Associated subunits (Human)
Kv β1 and Kv β2
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
bupivacaine Hs 5.4 pKd - - 7
quinidine Hs 5.2 pKd - - 30
resiniferatoxin Hs 4.6 pKd - - 8
nifedipine Hs 4.1 pKd - - 8
flecainide Hs 4.0 pKd - - 8
clofilium Hs 6.9 pIC50 - - 16
S9947 Hs 6.4 pIC50 - - 2,13
propafenone Hs 5.4 pIC50 - - 9
Pore Blocker Comments
Dilitiazem (pKd 3.9), 4-AP (pKd 3.6), TEA (pKd 0.5) [8]
Tissue Distribution
Insulinoma and islet
Species:  Human
Technique:  RT-PCR
References:  12,23
Atrial Myocytes, atrium, ventricle
Species:  Human
Technique:  RT-PCR
References:  12,25-26,35,39
Skeletal muscle
Species:  Mouse
Technique:  Northern Blot
References:  19
Pulmonary arterial smooth muscle, spinal cord.
Species:  Rat
Technique:  RT-PCR
References:  21,38,43
Brain: hippocampus, cortex, pituitary, oligodendrocytes, microglia, Schwann cells.
Species:  Rat
Technique:  Immunocytochemistry, RT-PCR, cDNA clone
References:  4,14,32-34
Heart
Species:  Rat
Technique:  Northern Blot
References:  19,27
Functional Assays
Molecular clone and voltage clamp
Species:  Human
Tissue:  MEL cells, atrial/ventricular myocytes, mouse L cell line
Response measured:  Ultrarapid-activating K+ current.
References:  6,8,29
Physiological Functions
Maintains membrane potential that modulates electrical excitability in neurons
Species:  Human
Tissue:  Atrial / ventricular myocytes
References:  6,8,29
Kv1.5 has properties similar to the ultrarapidly activating IKur current in the heart. Antisensetargeting Kv1.5 supresses IKur currents by almost 50%.
Species:  Human
Tissue:  Atrial / Ventricular myocytes
References:  6,29
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd		 MGI:96662  MP:0000350 abnormal cell proliferation PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd		 MGI:96662  MP:0000136 abnormal microglial cell morphology PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd		 MGI:96662  MP:0002272 abnormal nervous system electrophysiology PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd		 MGI:96662  MP:0003957 abnormal nitric oxide homeostasis PMID: 17055293 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6		 MGI:96662  MP:0005595 abnormal vascular smooth muscle physiology PMID: 11481235 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd		 MGI:96662  MP:0003488 decreased channel response intensity PMID: 17055293 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6		 MGI:96662  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 11349004 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6		 MGI:96662  MP:0003026 decreased vasoconstriction PMID: 11481235 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Chronic / Persistant Atrial Fibrillation
OMIM:  608583, 612240
Orphanet:  334
Therapeutic use:  Potential use in management of atrial fibrillation, via blockade of IKur
References:  3,37
Mutations not determined
Gene Expression and Pathophysiology
Down regulation of mRNA expression and protein synthesis of BKca and Kv1.5, caused by chronic cigarette smoking
Tissue or cell type:  Bronchial and bronchiolar smooth muscles
Pathophysiology: 
Species:  Rat
Technique: 
References:  42
Kv1.5 mRNA levels are dramatically repressed
Tissue or cell type:  Rat hypertrophied ventricles
Pathophysiology:  Altered K+ conductance; possibly responsible for prolonged duration of action potential recorded in hypertrophied ventricles
Species:  Rat
Technique:  RT-PCR, Northern Blotting
References:  20
Expression of Kv1.5 protein reduced by >50% in both the left and the right atrial appendages of AF patients.
Tissue or cell type:  Atrial appendages from patients with AF
Pathophysiology:  Kv1.5 thought to underlie the major component of the ultrarapid delayed rectifier K+ current, IKur
Species:  Human
Technique:  Semi-quantitive PCR, western blotting
References:  37

REFERENCES

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1. Albrecht, B; Weber, K; Pongs, O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept. Channels, 3 (3): 213-20. [PMID:8821794]

2. Bachmann, A; Gutcher, I; Kopp, K; Brendel, J; Bosch, RF; Busch, AE; Gögelein, H. (2001) Characterization of a novel Kv1.5 channel blocker in Xenopus oocytes, CHO cells, human and rat cardiomyocytes. Naunyn Schmiedebergs Arch. Pharmacol., 364 (5): 472-8. [PMID:11692231]

3. Brundel, BJ; Van Gelder, IC; Henning, RH; Tuinenburg, AE; Wietses, M; Grandjean, JG; Wilde, AA; Van Gilst, WH; Crijns, HJ. (2001) Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J. Am. Coll. Cardiol., 37 (3): 926-32. [PMID:11693772]

4. Chittajallu, R; Chen, Y; Wang, H; Yuan, X; Ghiani, CA; Heckman, T; McBain, CJ; Gallo, V. (2002) Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc. Natl. Acad. Sci. U.S.A., 99 (4): 2350-5. [PMID:11854528]

5. Curran, ME; Landes, GM; Keating, MT. (1992) Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Genomics, 12 (4): 729-37. [PMID:1349297]

6. Feng, J; Wible, B; Li, GR; Wang, Z; Nattel, S. (1997) Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ. Res., 80 (4): 572-9. [PMID:9118489]

7. Franqueza, L; Longobardo, M; Vicente, J; Delpón, E; Tamkun, MM; Tamargo, J; Snyders, DJ; Valenzuela, C. (1997) Molecular determinants of stereoselective bupivacaine block of hKv1.5 channels. Circ. Res., 81 (6): 1053-64. [PMID:9400387]

8. Grissmer, S; Nguyen, AN; Aiyar, J; Hanson, DC; Mather, RJ; Gutman, GA; Karmilowicz, MJ; Auperin, DD; Chandy, KG. (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol., 45 (6): 1227-34. [PMID:7517498]

9. Gutman, GA; Chandy, KG; Grissmer, S; Lazdunski, M; McKinnon, D; Pardo, LA; Robertson, GA; Rudy, B; Sanguinetti, MC; Stühmer, W; Wang, X. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol. Rev., 57 (4): 473-508. [PMID:16382104]

10. Heinemann, SH; Rettig, J; Graack, HR; Pongs, O. (1996) Functional characterization of Kv channel beta-subunits from rat brain. J. Physiol. (Lond.), 493 ( Pt 3): 625-33. [PMID:8799886]

11. Holmes, TC; Fadool, DA; Ren, R; Levitan, IB. (1996) Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science, 274 (5295): 2089-91. [PMID:8953041]

12. Kamb, A; Weir, M; Rudy, B; Varmus, H; Kenyon, C. (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. Proc. Natl. Acad. Sci. U.S.A., 86 (12): 4372-6. [PMID:2734290]

13. Knobloch, K; Brendel, J; Peukert, S; Rosenstein, B; Busch, AE; Wirth, KJ. (2002) Electrophysiological and antiarrhythmic effects of the novel I(Kur) channel blockers, S9947 and S20951, on left vs. right pig atrium in vivo in comparison with the I(Kr) blockers dofetilide, azimilide, d,l-sotalol and ibutilide. Naunyn Schmiedebergs Arch. Pharmacol., 366 (5): 482-7. [PMID:12382079]

14. Kotecha, SA; Schlichter, LC. (1999) A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation. J. Neurosci., 19 (24): 10680-93. [PMID:10594052]

15. Leicher, T; Bähring, R; Isbrandt, D; Pongs, O. (1998) Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J. Biol. Chem., 273 (52): 35095-101. [PMID:9857044]

16. Malayev, AA; Nelson, DJ; Philipson, LH. (1995) Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel. Mol. Pharmacol., 47 (1): 198-205. [PMID:7838129]

17. Martens, JR; Sakamoto, N; Sullivan, SA; Grobaski, TD; Tamkun, MM. (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J. Biol. Chem., 276 (11): 8409-14. [PMID:11115511]

18. Maruoka, ND; Steele, DF; Au, BP; Dan, P; Zhang, X; Moore, ED; Fedida, D. (2000) alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS Lett., 473 (2): 188-94. [PMID:10812072]

19. Matsubara, H; Liman, ER; Hess, P; Koren, G. (1991) Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles. J. Biol. Chem., 266 (20): 13324-8. [PMID:1712780]

20. Matsubara, H; Suzuki, J; Inada, M. (1993) 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. J. Clin. Invest., 92 (4): 1659-66. [PMID:7691883]

21. Matus-Leibovitch, N; Vogel, Z; Ezra-Macabee, V; Etkin, S; Nevo, I; Attali, B. (1996) Chronic morphine administration enhances the expression of Kv1.5 and Kv1.6 voltage-gated K+ channels in rat spinal cord. Brain Res. Mol. Brain Res., 40 (2): 261-70. [PMID:8872310]

22. Murata, M; Buckett, PD; Zhou, J; Brunner, M; Folco, E; Koren, G. (2001) SAP97 interacts with Kv1.5 in heterologous expression systems. Am. J. Physiol. Heart Circ. Physiol., 281 (6): H2575-84. [PMID:11709425]

23. Philipson, LH; Hice, RE; Schaefer, K; LaMendola, J; Bell, GI; Nelson, DJ; Steiner, DF. (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc. Natl. Acad. Sci. U.S.A., 88 (1): 53-7. [PMID:1986382]

24. Phromchotikul, T; Browne, DL; Curran, ME; Keating, MT; Litt, M. (1993) Dinucleotide repeat polymorphism at the KCNA5 locus. Hum. Mol. Genet., 2 (9): 1512. [PMID:8242092]

25. Ramashwami M, Gautam M, Kamb AA, Rudy B, Tanouye MA, Mathew MK. (1990) Human Potassium Channel Genes: Molecular CLoning and Functional Expression. Molecular Cell Neuroscience, volume (1): 214 - 223.

26. Rampe, D; Wang, Z; Fermini, B; Wible, B; Dage, RC; Nattel, S. (1995) Voltage- and time-dependent block by perhexiline of K+ currents in human atrium and in cells expressing a Kv1.5-type cloned channel. J. Pharmacol. Exp. Ther., 274 (1): 444-9. [PMID:7616429]

27. Roberds, SL; Tamkun, MM. (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc. Natl. Acad. Sci. U.S.A., 88 (5): 1798-802. [PMID:1705709]

28. Sewing, S; Roeper, J; Pongs, O. (1996) Kv beta 1 subunit binding specific for shaker-related potassium channel alpha subunits. Neuron, 16 (2): 455-63. [PMID:8789960]

29. Snyders, DJ; Tamkun, MM; Bennett, PB. (1993) A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J. Gen. Physiol., 101 (4): 513-43. [PMID:8505626]

30. Snyders, J; Knoth, KM; Roberds, SL; Tamkun, MM. (1992) Time-, voltage-, and state-dependent block by quinidine of a cloned human cardiac potassium channel. Mol. Pharmacol., 41 (2): 322-30. [PMID:1538710]

31. Sobko, A; Peretz, A; Attali, B. (1998) Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. EMBO J., 17 (16): 4723-34. [PMID:9707431]

32. Sobko, A; Peretz, A; Shirihai, O; Etkin, S; Cherepanova, V; Dagan, D; Attali, B. (1998) Heteromultimeric delayed-rectifier K+ channels in schwann cells: developmental expression and role in cell proliferation. J. Neurosci., 18 (24): 10398-408. [PMID:9852577]

33. Swanson, R; Marshall, J; Smith, JS; Williams, JB; Boyle, MB; Folander, K; Luneau, CJ; Antanavage, J; Oliva, C; Buhrow, SA. (1990) Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron, 4 (6): 929-39. [PMID:2361015]

34. Takimoto, K; Fomina, AF; Gealy, R; Trimmer, JS; Levitan, ES. (1993) Dexamethasone rapidly induces Kv1.5 K+ channel gene transcription and expression in clonal pituitary cells. Neuron, 11 (2): 359-69. [PMID:8352944]

35. Tamkun, MM; Knoth, KM; Walbridge, JA; Kroemer, H; Roden, DM; Glover, DM. (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J., 5 (3): 331-7. [PMID:2001794]

36. Uebele, VN; England, SK; Chaudhary, A; Tamkun, MM; Snyders, DJ. (1996) Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta 2.1 subunits. J. Biol. Chem., 271 (5): 2406-12. [PMID:8576199]

37. Van Wagoner, DR; Pond, AL; McCarthy, PM; Trimmer, JS; Nerbonne, JM. (1997) Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ. Res., 80 (6): 772-81. [PMID:9168779]

38. Wang, J; Juhaszova, M; Rubin, LJ; Yuan, XJ. (1997) Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells. J. Clin. Invest., 100 (9): 2347-53. [PMID:9410914]

39. Wang, Z; Fermini, B; Nattel, S. (1993) Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ. Res., 73 (6): 1061-76. [PMID:8222078]

40. Wang, Z; Kiehn, J; Yang, Q; Brown, AM; Wible, BA. (1996) Comparison of binding and block produced by alternatively spliced Kvbeta1 subunits. J. Biol. Chem., 271 (45): 28311-7. [PMID:8910452]

41. Wible, BA; Yang, Q; Kuryshev, YA; Accili, EA; Brown, AM. (1998) Cloning and expression of a novel K+ channel regulatory protein, KChAP. J. Biol. Chem., 273 (19): 11745-51. [PMID:9565597]

42. Ye, H; Ma, WL; Yang, ML; Liu, SY; Wang, DX. (2004) Effect of chronic cigarette smoking on large-conductance calcium-activated potassium channel and Kv1.5 expression in bronchial smooth muscle cells of rats. , 56 (5): 573-8. [PMID:15497036]

43. Yuan, XJ; Wang, J; Juhaszova, M; Golovina, VA; Rubin, LJ. (1998) Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am. J. Physiol., 274 (4 Pt 1): L621-35. [PMID:9575881]

To cite this database page, please use the following:

K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Bernardo Rudy, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv1.5. Last modified on 23/01/2012. Accessed on 19/06/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=542.


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