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Kv1.2

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
Gene Expression and Pathophysiology
General Comments
References
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, shaker-related subfamily, member 2 6,16
Mouse 6 1 499 3 F2.3 Kcna2 potassium voltage-gated channel, shaker-related subfamily, member 2
Rat 6 1 499 2q34 Kcna2 potassium voltage-gated channel, shaker-related subfamily, member 2
Previous and Unofficial Names
HuK (IV)
MK2
BK2
RCK5
RAK
BGK5
XSha2
NGK1
HBK51
Kv1.2
HK4
Potassium (K+) channel protein alpha 2 voltage dependent
Potassium (K+) channel protein alpha 2, voltage dependent
Potassium voltage gated channel shaker related subfamily member 2
RBK2
potassium voltage gated channel, shaker related subfamily, member 2
potassium voltage-gated channel subfamily A member 2
potassium voltage-gated channel, shaker-related subfamily, member 2
voltage-gated potassium channel subunit Kv1.2
Mk-2
Kca1-2
Akr6a4
Database Links
ChEMBL Target 10552 (Hs), 100471 (Mm)
Ensembl ENSG00000177301 (Hs), ENSMUSG00000040724 (Mm), ENSRNOG00000018285 (Rn)
Entrez Gene 3737 (Hs), 16490 (Mm), 25468 (Rn)
GeneCards KCNA2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcna2 (Mm)
HomoloGene 21034 (Hs)
Human Protein Reference Database 01443 (Hs)
InterPro P16389 (Hs), P63141 (Mm), P63142 (Rn)
KEGG Gene hsa:3737 (Hs), mmu:16490 (Mm), rno:25468 (Rn)
OMIM 176262 (Hs)
PharmGKB Gene PA206 (Hs)
PhosphoSitePlus P16389 (Hs), P15386 (Mm), P63142 (Rn)
Protein Ontology (PRO) PRO:000000810 (Hs)
RefSeq Nucleotide NM_004974 (Hs), NM_008417 (Mm), NM_012970 (Rn)
RefSeq Protein NP_004965 (Hs), NP_032443 (Mm), NP_037102 (Rn)
TreeFam ENSG00000177301 (Hs), ENSMUSG00000040724 (Mm), ENSRNOG00000018285 (Rn)
UniGene Hs. 248139 (Hs)
UniProt P16389 (Hs), P63141 (Mm), P63142 (Rn)
Wikipedia Kv1.2
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated potassium channels Kv1.2 Search by accession number: P63142, P63141, P16389
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kvβ1 22,24,26
Kvβ2 23-24,27
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PSD95 9
RhoA 2
Caspr2 18
SAP97 32
SNAP95 32
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [14.0 - 18.0 pS]
References:  7
Species:  Mouse
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  7
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  5.0 – 27.0 6.0 7,21 B82 mouse fibroblasts Mouse
Inactivation  -15.0 - 7
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
hongotoxin-1 Rn 12.6 – 13.0 pKd - - 12
noxiustoxin Rn 8.7 pKd - - 7
charybdotoxin Rn 7.9 pKd - - 7
dendrotoxin-1 Rn 7.8 pKd - - 7
α-KTx 13.2 Rn 7.0 pKd - - 5
pandinotoxin-K α Rn 10.5 pIC50 - - 8,25
BgK Rn 7.6 pIC50 - - 4
mast cell degranulating peptide Rn 6.4 pIC50 - - 8
Pore Blocker Comments
Anandamide pKd= 5.6 [19], capsaicin pKd= 4.3, resiniferatoxin pKd= 4.5, flecanide pKd= 3.7, nifedipine pKd=4.7, diltazem pKd=3.7, tetraethylammonium pKd=0.3, 4-aminopyridine pKd=3.2 [7], [8], [35]
Tissue Distribution
Retina
Species:  Mouse
Technique:  RT-PCR
References:  10-11
Schwann cells and sciatic nerve
Species:  Mouse
Technique:  Oligonucleic probes
References:  1,30
Brain
Species:  Mouse
Technique:  In situ hybridisation
References:  3
Spinal cord
Species:  Mouse
Technique:  Immunohistochemistry, western blotting
References:  28
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:  RT-PCR
References:  15,31
Skeletal and cardiac muscles
Species:  Rat
Technique:  Northern Blot
References:  14
Retina, islet
Species:  Rat
Technique:  RT-PCR
References:  8
Functional Assays
Molecular clone and voltage clamp
Species:  Rat
Tissue:  Xenopus leavis Oocytes
Response measured:  Delayed rectifier potassium currents
References:  7,31
Physiological Functions
Maintaining membrane potential, modulating electrical excitability in neurons and muscle.
Species:  Rat
Tissue:  CNS and muscle
References:  7-8,14,20,28-29,31,36
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

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:  Heart, hippocampus
Pathophysiology:  Seizure activity caused a reduction of Kv1.2 and Kv4.2 mRNAs in the dentate granule cells of the hippocampus.
Acute and chronic electroconvulsive shock reduces Kv1.2 and Kv4.2 mRNA abundance.
Hypoxia inhibits gene expression of Kv1.2 in pulmonary artery smooth muscle cells.
Kv1.2 mRNA downregulated in rat heart with right ventricular hypertrophy.
Species:  Rat
Technique: 
References:  13,17,33-34
General Comments
Kv1.2 can coassemble with other Kv1 family members in heteromultimers but not with members of other Kv families. It is unique in that it has an intronless coding region.

REFERENCES

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1. Black, JA; Waxman, SG; Smith, KJ. (2006) Remyelination of dorsal column axons by endogenous Schwann cells restores the normal pattern of Nav1.6 and Kv1.2 at nodes of Ranvier. Brain, 129 (Pt 5): 1319-29. [PMID:16537565]

2. 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]

3. 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]

4. 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]

5. 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]

6. Grissmer, S; Dethlefs, B; Wasmuth, JJ; Goldin, AL; Gutman, GA; Cahalan, MD; Chandy, KG. (1990) Expression and chromosomal localization of a lymphocyte K+ channel gene. Proc. Natl. Acad. Sci. U.S.A., 87 (23): 9411-5. [PMID:2251283]

7. 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]

8. 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]

9. 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]

10. Klumpp, DJ; Song, EJ; Ito, S; Sheng, MH; Jan, LY; Pinto, LH. (1995) The Shaker-like potassium channels of the mouse rod bipolar cell and their contributions to the membrane current. J. Neurosci., 15 (7 Pt 1): 5004-13. [PMID:7623129]

11. 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]

12. 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]

13. Lee, JK; Nishiyama, A; Kambe, F; Seo, H; Takeuchi, S; Kamiya, K; Kodama, I; Toyama, J. (1999) Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy. Am. J. Physiol., 277 (5 Pt 2): H1725-31. [PMID:10564125]

14. 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]

15. 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]

16. Minor, DL; Lin, YF; Mobley, BC; Avelar, A; Jan, YN; Jan, LY; Berger, JM. (2000) The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Cell, 102 (5): 657-70. [PMID:11007484]

17. Pei, Q; Burnet, PW; Grahame-Smith, DG; Zetterström, TS. (1997) Differential effects of acute and chronic electroconvulsive shock on the abundance of messenger RNAs for voltage-dependent potassium channel subunits in the rat brain. Neuroscience, 78 (2): 343-50. [PMID:9145791]

18. 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]

19. 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]

20. 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.

21. 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.

22. 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]

23. 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]

24. 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]

25. Rogowski, RS; Collins, JH; O'Neill, TJ; Gustafson, TA; Werkman, TR; Rogawski, MA; Tenenholz, TC; Weber, DJ; Blaustein, MP. (1996) Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels. Mol. Pharmacol., 50 (5): 1167-77. [PMID:8913348]

26. 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]

27. Shi, G; Nakahira, K; Hammond, S; Rhodes, KJ; Schechter, LE; Trimmer, JS. (1996) Beta subunits promote K+ channel surface expression through effects early in biosynthesis. Neuron, 16 (4): 843-52. [PMID:8608002]

28. Sinha, K; Karimi-Abdolrezaee, S; Velumian, AA; Fehlings, MG. (2006) Functional changes in genetically dysmyelinated spinal cord axons of shiverer mice: role of juxtaparanodal Kv1 family K+ channels. J. Neurophysiol., 95 (3): 1683-95. [PMID:16319208]

29. 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]

30. 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]

31. 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]

32. 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]

33. Tsaur, ML; Sheng, M; Lowenstein, DH; Jan, YN; Jan, LY. (1992) Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. Neuron, 8 (6): 1055-67. [PMID:1610565]

34. 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]

35. Wulff, H; Rauer, H; Düring, T; Hanselmann, C; Ruff, K; Wrisch, A; Grissmer, S; Hänsel, W. (1998) Alkoxypsoralens, novel nonpeptide blockers of Shaker-type K+ channels: synthesis and photoreactivity. J. Med. Chem., 41 (23): 4542-9. [PMID:9804693]

36. Yazulla, S; Studholme, KM. (1998) Differential distribution of Shaker-like and Shab-like K+-channel subunits in goldfish retina and retinal bipolar cells. J. Comp. Neurol., 396 (1): 131-40. [PMID:9623892]

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: Kv1.2. Last modified on 11/10/2012. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=539.


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