K<SUB>v</SUB>1.2 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv1.2

Target id: 539

Nomenclature: Kv1.2

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 Kv1.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 499 1p13 KCNA2 potassium voltage-gated channel subfamily A member 2
Mouse 6 1 499 3 F2.3 Kcna2 potassium voltage-gated channel, shaker-related subfamily, member 2 16,31
Rat 6 1 499 2q34 Kcna2 potassium voltage-gated channel subfamily A member 2
Previous and Unofficial Names
BGK5 | BK2 | HBK51 | MK2 | NGK1 | RAK | RCK5 | HK4 | Potassium (K+) channel protein alpha 2 voltage dependent | potassium voltage-gated channel subfamily A member 2 | RBK2 | XSha2 | potassium channel, voltage gated shaker related subfamily A, member 2 | 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 3,7,28,35
Kv1.4 3,7,28,35
Auxiliary Subunits
Name References
Kvβ1 3,26,28-29
Kvβ2 3,26,28,30
Other Associated Proteins
Name References
PSD95 3,15,33
Caspr2 22
RhoA 5
SAP97 33
Cortactin 12
ADAM22 21
Functional Characteristics
KV
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [14.0 - 18.0 pS]
References:  10
Species:  Mouse
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  10
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  5.0 – 27.0 6.0 10 B82 mouse fibroblasts Mouse
Inactivation  -15.0 - 10
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -27.1 - 13 Xenopus laevis oocyte Mouse
Inactivation  -37.1 3559.0 13

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
hongotoxin-1 Rn - 12.6 – 13.0 pKd - - 18
pKd 12.6 – 13.0 [18]
noxiustoxin Rn - 8.7 pKd - - 10
pKd 8.7 (Kd 2x10-9 M) [10]
charybdotoxin Rn - 7.9 pKd - - 10
pKd 7.9 [10]
dendrotoxin-I Rn - 7.8 pKd - - 10
pKd 7.8 [10]
α-KTx 13.2 Rn - 7.0 pKd - - 9
pKd 7.0 [9]
nifedipine Rn Pore blocker 4.7 pKd - - 10
pKd 4.7 (Kd 1.8x10-5 M) [10]
resiniferatoxin Rn Pore blocker 4.5 pKd - - 10
pKd 4.5 (Kd 3.1x10-5 M) [10]
capsaicin Rn Pore blocker 4.4 pKd - - 10
pKd 4.4 (Kd 4.5x10-5 M) [10]
diltiazem Rn Pore blocker 3.7 pKd - - 10
pKd 3.7 (Kd 1.87x10-4 M) [10]
flecainide Rn Pore blocker 3.7 pKd - - 10
pKd 3.7 (Kd 2.17x10-4 M) [10]
fampridine Rn Pore blocker 3.2 pKd - - 10
pKd 3.2 (Kd 5.9x10-4 M) [10]
margatoxin Hs Inhibition 11.2 pIC50 - - 1
pIC50 11.2 (IC50 6.4x10-12 M) [1]
pandinotoxin-K α Rn - 10.5 pIC50 - - 9
pIC50 10.5 [9]
α-dendrotoxin Rn - 7.8 – 9.4 pIC50 - - 10,14
pIC50 7.8 – 9.4 (IC50 1.7x10-8 – 3.8x10-10 M) [10,14]
BgK Rn - 7.6 pIC50 - - 8
pIC50 7.6 [8]
mast cell degranulating peptide Rn - 6.4 pIC50 - - 10
pIC50 6.4 [10]
anandamide Hs Pore blocker 5.6 pIC50 - - 23
pIC50 5.6 (IC50 2.7x10-6 M) [23]
View species-specific channel blocker tables
Channel Blocker Comments
IC50 for α-dendrotoxin blockade differs between Kv1.2 expressed in Xenopus oocytes and mammalian cells [11]. Kv1.2 and Kv1.5 are resistant to tetraethylammonium [10].
Tissue Distribution
Sciatic nerve
Species:  Mouse
Technique:  Immunohistochemistry
References:  25
Brain
Species:  Mouse
Technique:  In situ hybridisation
References:  6
Spinal cord
Species:  Mouse
Technique:  Immunohistochemistry, western blotting
References:  24
Retina
Species:  Mouse
Technique:  Northern blot, immunohistochemistry
References:  17
Brain
Species:  Mouse
Technique:  Immunohistochemistry
References:  35
Brain
Species:  Rat
Technique:  Immunohistochemistry
References:  27,34
Brain (pons, medulla, cerebellum, inferior colliculus > hippocampus, thalamus, cerebral cortex, superior colliculus > midbrain, corpus striatum, olfactory bulb)(neurons associated with mechanoreception and proprioception)
Species:  Rat
Technique:  In situ hybridisation
References:  2,20
Skeletal and cardiac muscles
Species:  Rat
Technique:  Northern Blot
References:  19
Functional Assays
Molecular cloning and voltage clamp
Species:  Rat
Tissue:  Xenopus leavis Oocytes
Response measured:  Delayed rectifier potassium currents
References:  10,32
Physiological Functions
Maintaining membrane potential, modulating electrical excitability in neurons. Deletion leads to early postnatal mortality.
Species:  Mouse
Tissue:  CNS
References:  4
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0005402 abnormal action potential PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd
MGI:96659  MP:0004994 abnormal brain wave pattern PMID: 17925011 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0003484 abnormal channel response PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0002272 abnormal nervous system electrophysiology PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd
MGI:96659  MP:0001501 abnormal sleep pattern PMID: 17925011 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0001957 apnea PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd
MGI:96659  MP:0001265 decreased body size PMID: 17925011 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0001262 decreased body weight PMID: 17634333 
Kcna2+|Kcna2tm1Tem Kcna2tm1Tem/Kcna2+
C3Fe.129S7-Kcna2
MGI:96659  MP:0002578 impaired ability to fire action potentials PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0002578 impaired ability to fire action potentials PMID: 17634333 
Kcna2+|Kcna2tm1Tem Kcna2tm1Tem/Kcna2+
C3Fe.129S7-Kcna2
MGI:96659  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd * C57BL/6
MGI:96659  MP:0002082 postnatal lethality PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0002082 postnatal lethality PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd
MGI:96659  MP:0002082 postnatal lethality PMID: 17925011 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd
MGI:96659  MP:0002064 seizures PMID: 17925011 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
involves: 129S7/SvEvBrd * C57BL/6
MGI:96659  MP:0002826 tonic seizures PMID: 17634333 
Kcna2tm1Tem Kcna2tm1Tem/Kcna2tm1Tem
C3Fe.129S7-Kcna2
MGI:96659  MP:0002826 tonic seizures PMID: 17634333 
Gene Expression and Pathophysiology
Decrease
Tissue or cell type:  Cerebellum
Pathophysiology:  I402T mutation leads to ataxia
Species:  Rat
Technique: 
References:  36
Biologically Significant Variant Comments
A total of 751 SNPs have been identified in human KCNA2. For more information see GeneCards.
General Comments
Kv1.2 can coassembles with other Kv1 family members, most prominently Kv1.1 and Kv1.4, in heteromultimers found on axons of brain neurons. Also expressed in DRG neurons but not with members of other Kv families. It is unique in that it has an intronless coding region. Kv1.2 KO mice die in the third postnatal week.

References

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1. Bartok A, Toth A, Somodi S, Szanto TG, Hajdu P, Panyi G, Varga Z. (2014) Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels. Toxicon, 87: 6-16. [PMID:24878374]

2. Beckh S, Pongs O. (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J., 9 (3): 777-82. [PMID:2311579]

3. Bildl W, Haupt A, Müller CS, Biniossek ML, Thumfart JO, Hüber B, Fakler B, Schulte U. (2012) Extending the dynamic range of label-free mass spectrometric quantification of affinity purifications. Mol. Cell Proteomics, 11 (2): M111.007955. [PMID:22067099]

4. Brew HM, Gittelman JX, Silverstein RS, Hanks TD, Demas VP, Robinson LC, Robbins CA, McKee-Johnson J, Chiu SY, Messing A et al.. (2007) Seizures and reduced life span in mice lacking the potassium channel subunit Kv1.2, but hypoexcitability and enlarged Kv1 currents in auditory neurons. J. Neurophysiol., 98 (3): 1501-25. [PMID:17634333]

5. Cachero TG, Morielli AD, Peralta EG. (1998) The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel. Cell, 93 (6): 1077-85. [PMID:9635436]

6. Chandy KG, Williams CB, Spencer RH, Aguilar BA, Ghanshani S, Tempel BL, Gutman GA. (1990) A family of three mouse potassium channel genes with intronless coding regions. Science, 247 (4945): 973-5. [PMID:2305265]

7. Coleman SK, Newcombe J, Pryke J, Dolly JO. (1999) Subunit composition of Kv1 channels in human CNS. J. Neurochem., 73 (2): 849-58. [PMID:10428084]

8. Cotton J, Crest M, Bouet F, Alessandri N, Gola M, Forest E, Karlsson E, Castañeda O, Harvey AL, Vita C, Ménez A. (1997) A potassium-channel toxin from the sea anemone Bunodosoma granulifera, an inhibitor for Kv1 channels. Revision of the amino acid sequence, disulfide-bridge assignment, chemical synthesis, and biological activity. Eur. J. Biochem., 244 (1): 192-202. [PMID:9063464]

9. Dudina EE, Korolkova YV, Bocharova NE, Koshelev SG, Egorov TA, Huys I, Tytgat J, Grishin EV. (2001) OsK2, a new selective inhibitor of Kv1.2 potassium channels purified from the venom of the scorpion Orthochirus scrobiculosus. Biochem. Biophys. Res. Commun., 286 (5): 841-7. [PMID:11527374]

10. 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]

11. Harvey AL. (2001) Twenty years of dendrotoxins. Toxicon, 39 (1): 15-26. [PMID:10936620]

12. Hattan D, Nesti E, Cachero TG, Morielli AD. (2002) Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin. J. Biol. Chem., 277 (41): 38596-606. [PMID:12151401]

13. Hopkins WF, Allen ML, Houamed KM, Tempel BL. (1994) Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1. Pflugers Arch., 428 (3-4): 382-90. [PMID:7816560]

14. Hurst RS, Busch AE, Kavanaugh MP, Osborne PB, North RA, Adelman JP. (1991) Identification of amino acid residues involved in dendrotoxin block of rat voltage-dependent potassium channels. Mol. Pharmacol., 40 (4): 572-6. [PMID:1921987]

15. Kim E, Niethammer M, Rothschild A, Jan YN, Sheng M. (1995) Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases. Nature, 378 (6552): 85-8. [PMID:7477295]

16. Klocke R, Roberds SL, Tamkun MM, Gronemeier M, Augustin A, Albrecht B, Pongs O, Jockusch H. (1993) Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal. Genomics, 18 (3): 568-74. [PMID:7905852]

17. Klumpp DJ, Song EJ, Pinto LH. (1995) Identification and localization of K+ channels in the mouse retina. Vis. Neurosci., 12 (6): 1177-90. [PMID:8962835]

18. 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]

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. McKinnon D. (1989) Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. J. Biol. Chem., 264 (14): 8230-6. [PMID:2722779]

21. Ogawa Y, Oses-Prieto J, Kim MY, Horresh I, Peles E, Burlingame AL, Trimmer JS, Meijer D, Rasband MN. (2010) ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons. J. Neurosci., 30 (3): 1038-48. [PMID:20089912]

22. 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]

23. Poling JS, Rogawski MA, Salem N, Vicini S. (1996) Anandamide, an endogenous cannabinoid, inhibits Shaker-related voltage-gated K+ channels. Neuropharmacology, 35 (7): 983-91. [PMID:8938728]

24. Rasband MN, Trimmer JS. (2001) Subunit composition and novel localization of K+ channels in spinal cord. J. Comp. Neurol., 429 (1): 166-76. [PMID:11086297]

25. Rasband MN, Trimmer JS, Schwarz TL, Levinson SR, Ellisman MH, Schachner M, Shrager P. (1998) Potassium channel distribution, clustering, and function in remyelinating rat axons. J. Neurosci., 18 (1): 36-47. [PMID:9412484]

26. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, Pongs O. (1994) Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit. Nature, 369 (6478): 289-94. [PMID:8183366]

27. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, Trimmer JS. (1995) Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain. J. Neurosci., 15 (7 Pt 2): 5360-71. [PMID:7623158]

28. 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]

29. Schulte U, Thumfart JO, Klöcker N, Sailer CA, Bildl W, Biniossek M, Dehn D, Deller T, Eble S, Abbass K et al.. (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron, 49 (5): 697-706. [PMID:16504945]

30. Scott VE, Rettig J, Parcej DN, Keen JN, Findlay JB, Pongs O, Dolly JO. (1994) Primary structure of a beta subunit of alpha-dendrotoxin-sensitive K+ channels from bovine brain. Proc. Natl. Acad. Sci. U.S.A., 91 (5): 1637-41. [PMID:8127858]

31. Street VA, Tempel BL. (1997) Physical mapping of potassium channel gene clusters on mouse chromosomes three and six. Genomics, 44 (1): 110-7. [PMID:9286706]

32. Stühmer W, Ruppersberg JP, Schröter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O. (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J., 8 (11): 3235-44. [PMID:2555158]

33. Tiffany AM, Manganas LN, Kim E, Hsueh YP, Sheng M, Trimmer JS. (2000) PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. J. Cell Biol., 148 (1): 147-58. [PMID:10629225]

34. Veh RW, Lichtinghagen R, Sewing S, Wunder F, Grumbach IM, Pongs O. (1995) Immunohistochemical localization of five members of the Kv1 channel subunits: contrasting subcellular locations and neuron-specific co-localizations in rat brain. Eur. J. Neurosci., 7 (11): 2189-205. [PMID:8563969]

35. Wang H, Kunkel DD, Martin TM, Schwartzkroin PA, Tempel BL. (1993) Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. Nature, 365 (6441): 75-9. [PMID:8361541]

36. Xie G, Harrison J, Clapcote SJ, Huang Y, Zhang JY, Wang LY, Roder JC. (2010) A new Kv1.2 channelopathy underlying cerebellar ataxia. J. Biol. Chem., 285 (42): 32160-73. [PMID:20696761]

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: Kv1.2. Last modified on 20/10/2015. Accessed on 17/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=539.