K<SUB>v</SUB>1.6 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv1.6

Target id: 543

Nomenclature: Kv1.6

Family: Voltage-gated potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for Kv1.6 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 529 12p13.3 KCNA6 potassium voltage-gated channel subfamily A member 6 1,5
Mouse 6 1 529 6 F3 Kcna6 potassium voltage-gated channel, shaker-related, subfamily, member 6 11
Rat 6 1 530 4q42 Kcna6 potassium voltage-gated channel subfamily A member 6 11
Previous and Unofficial Names
HBK2 | RCK2 | potassium voltage-gated channel subfamily A member 6 | potassium voltage gated channel, shaker related subfamily, member 6 | potassium voltage-gated channel, shaker-related subfamily, member 6 | potassium channel, voltage gated shaker related subfamily A, member 6 | potassium voltage-gated channel, shaker-related, subfamily, member 6 | potassium voltage-gated channel
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kv1.1 3
Kv1.2 3
Auxiliary Subunits
Name References
Kvβ1 14-15
Kvβ2 14-15
Other Associated Proteins
Name References
Caspr2 12
Functional Characteristics
KV
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [9.0 pS]
References:  5
Species:  Human
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  5
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -20.0 - 5 Xenopus laevis oocyte Human
Inactivation  - 3200.0 5
Associated subunits (Human)
Kv β1 and Kv β2

Download all structure-activity data for this target as a CSV file

Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
[125I]BgK (W5Y / Y26F) Rn - 11.4 pKd - - 13
pKd 11.4 [13]
hongotoxin-1 Rn - 11.0 pKd - - 9
pKd 11.0 [9]
[125I]α-DTX Rn - 10.4 pKd - - 13
pKd 10.4 [13]
ShK Toxin Rn - 9.8 pIC50 - - 7
pIC50 9.8 [7]
charybdotoxin Hs - 9.0 pIC50 - - 5
pIC50 9.0 [5]
mast cell degranulating peptide Hs - 8.0 pIC50 - - 5
pIC50 8.0 [5]
α-dendrotoxin Hs - 7.7 pIC50 - - 5
pIC50 7.7 (IC50 1.99x10-8 M) [5]
conopeptide Y-PI1 Rn Pore blocker 6.8 pIC50 - - 6
pIC50 6.8 (IC50 1.7x10-7 M) [6]
tetraethylammonium Hs - 2.2 pIC50 - - 5
pIC50 2.2 (IC50 7x10-3 M) [5]
View species-specific channel blocker tables
Channel Blocker Comments
β-bungarotoxin (pIC50 6.7), 10-N-methylcarbamoyl-3, 7 -bis(dimethylamino)phenothiazine (pIC50 6.7), 4-AP (pIC50 6.7), p114a (pIC50 5.8) [5,18].
Tissue Distribution
Astrocytes.
Species:  Mouse
Technique:  Immunocytochemistry
References:  17
Spinal cord.
Species:  Rat
Technique:  In situ hybridisation
References:  10
Distal pulmonary artery, aorta, pulmonary artery smooth muscle cells.
Species:  Rat
Technique:  RT-PCR
References:  19,21
Oligodendrocytes, progenitor cells.
Species:  Rat
Technique:  In situ hybridisation
References:  2
Brain (medulla-pons, inferior colliculus > colliculus, midbrain > corpus striatum, cerebral cortex, hippocampus > cerebellum > olfactory bulb).
Species:  Rat
Technique:  Northern blot
References:  5
Myelinated adult optic nerve, murine colonic smooth muscle.
Species:  Rat
Technique:  RT-PCR, immunohistochemistry
References:  8,14
Functional Assays
Molecular clone and voltage clamp.
Species:  Human
Tissue:  Xenopus laevis oocytes.
Response measured:  Delayed rectifier current.
References:  5
Physiological Functions
Regulator of membrane potential neurons.
Species:  Rat
Tissue:  Nodose ganglia.
References:  4
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna6tm1Lex Kcna6tm1Lex/Kcna6tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:96663  MP:0001552 increased circulating triglyceride level
Kcna6tm1Lex Kcna6tm1Lex/Kcna6tm1Lex
involves: 129S5/SvEvBrd * C57BL/6J
MGI:96663  MP:0001973 increased thermal nociceptive threshold
Gene Expression and Pathophysiology
Decrease of Kv1.6 mRNA and protein expression
Tissue or cell type:  Distal pulmonary artery
Pathophysiology:  The mRNA and protein levels of Kv1.6 α-subunits reduced by 34.4% and 39.2% separately exposed to chronic hypoxia
Species:  Rat
Technique:  RT-PCR, Western Blotting
References:  20
Biologically Significant Variant Comments
A total of 1034 SNPs have been identified in human KCNA6. For more information please see the entry on GeneCards.
General Comments
Kv1.6 may co-assemble with other Kv1 family members in heteromultimers. It cannot, however, co-assemble with members of other Kv families. It has an intronless coding region. The N-terminus of the protein contains an N-terminus inactivation prevention (NIP) domain [16]

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. Attali B, Wang N, Kolot A, Sobko A, Cherepanov V, Soliven B. (1997) Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells. J. Neurosci., 17 (21): 8234-45. [PMID:9334399]

3. Dodson PD, Barker MC, Forsythe ID. (2002) Two heteromeric Kv1 potassium channels differentially regulate action potential firing. J. Neurosci., 22 (16): 6953-61. [PMID:12177193]

4. Glazebrook PA, Ramirez AN, Schild JH, Shieh CC, Doan T, Wible BA, Kunze DL. (2002) Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons. J. Physiol. (Lond.), 541 (Pt 2): 467-82. [PMID:12042352]

5. Grupe A, Schröter KH, Ruppersberg JP, Stocker M, Drewes T, Beckh S, Pongs O. (1990) Cloning and expression of a human voltage-gated potassium channel. A novel member of the RCK potassium channel family. EMBO J., 9 (6): 1749-56. [PMID:2347305]

6. Imperial JS, Chen P, Sporning A, Terlau H, Daly NL, Craik DJ, Alewood PF, Olivera BM. (2008) Tyrosine-rich conopeptides affect voltage-gated K+ channels. J. Biol. Chem., 283 (34): 23026-32. [PMID:18505731]

7. Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG. (1998) ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J. Biol. Chem., 273 (49): 32697-707. [PMID:9830012]

8. Koh SD, Ward SM, Dick GM, Epperson A, Bonner HP, Sanders KM, Horowitz B, Kenyon JL. (1999) Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle. J. Physiol. (Lond.), 515 ( Pt 2): 475-87. [PMID:10050014]

9. Koschak A, Bugianesi RM, Mitterdorfer J, Kaczorowski GJ, Garcia ML, Knaus HG. (1998) Subunit composition of brain voltage-gated potassium channels determined by hongotoxin-1, a novel peptide derived from Centruroides limbatus venom. J. Biol. Chem., 273 (5): 2639-44. [PMID:9446567]

10. 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]

11. Migeon MB, Street VA, Demas VP, Tempel BL. (1992) Cloning, sequence and chromosomal localization of MK6, a murine potassium channel gene. Epilepsy Res. Suppl., 9: 173-80; discussion 180-1. [PMID:1285906]

12. Poliak S, Gollan L, Martinez R, Custer A, Einheber S, Salzer JL, Trimmer JS, Shrager P, Peles E. (1999) Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron, 24 (4): 1037-47. [PMID:10624965]

13. Racapé J, Lecoq A, Romi-Lebrun R, Liu J, Kohler M, Garcia ML, Ménez A, Gasparini S. (2002) Characterization of a novel radiolabeled peptide selective for a subpopulation of voltage-gated potassium channels in mammalian brain. J. Biol. Chem., 277 (6): 3886-93. [PMID:11707459]

14. Rasband MN, Trimmer JS, Peles E, Levinson SR, Shrager P. (1999) K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve. J. Neurocytol., 28 (4-5): 319-31. [PMID:10739574]

15. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, Trimmer JS. (1997) Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J. Neurosci., 17 (21): 8246-58. [PMID:9334400]

16. Roeper J, Sewing S, Zhang Y, Sommer T, Wanner SG, Pongs O. (1998) NIP domain prevents N-type inactivation in voltage-gated potassium channels. Nature, 391 (6665): 390-3. [PMID:9450755]

17. Smart SL, Bosma MM, Tempel BL. (1997) Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes. Glia, 20 (2): 127-34. [PMID:9179597]

18. 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]

19. 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]

20. Wang J, Weigand L, Wang W, Sylvester JT, Shimoda LA. (2005) Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery. Am. J. Physiol. Lung Cell Mol. Physiol., 288 (6): L1049-58. [PMID:15665041]

21. 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]

Contributors

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How to cite this page

James S. Trimmer, 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: Kv1.6. Last modified on 14/10/2014. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=543.