K<SUB>v</SUB>3.2 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv3.2

Target id: 549

Nomenclature: Kv3.2

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 Kv3.2 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 613 12q14.1 KCNC2 potassium voltage-gated channel subfamily C member 2 4
Mouse 6 1 639 10 D2 Kcnc2 potassium voltage gated channel, Shaw-related subfamily, member 2 4
Rat 6 1 638 7q12-22 Kcnc2 potassium voltage-gated channel subfamily C member 2 10
Previous and Unofficial Names
Raw1 | potassium voltage-gated channel subfamily C member 2 | potassium voltage-gated channel, Shaw-related subfamily, member 2 | potassium channel, voltage gated Shaw related subfamily C, member 2 | potassium channel, voltage gated Shaw-related subfamily C, member 2 | potassium voltage gated channel
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
KV
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+ [16.0 - 20.0 pS]
References:  16
Species:  Rat
Macroscopic current rectification:  Delayed Rectifier Current
References:  16
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  13.0 - 10 Xenopus laevis Oocytes Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  13.0 4.0 16 Xenopus laevis Oocytes Rat
Inactivation  - -
Comments  Inactivation very slow.

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

Gating Inhibitor Comments
Sea Anemone Toxin BDS-I and BDS-II: At +40 mV, 500 nM BDS-I inhibited rat Kv3.2 by 48.1 ± 4.5% (n = 5), 500 nM BDS-II inhibited Kv3.2 by 52.5 ± 3.7% (n = 4) [25] Alanine substitution mutagenesis around the S3b and S4 segments of Kv3.2 revealed that BDS acts via voltage-sensing domains. [25]
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
verapamil Rn - 4.9 pEC50 - - 9
pEC50 4.9 [9]
ShK Toxin Hs - 9.5 pIC50 - - 24
pIC50 9.5 [24]
fampridine Rn - 4.6 pIC50 - - 7
pIC50 4.6 (IC50 2.4x10-5 M) [7]
tetraethylammonium Rn - 4.2 pIC50 - - 7
pIC50 4.2 (IC50 6.3x10-5 M) [7]
View species-specific channel blocker tables
Channel Blocker Comments
3-isobutyl-1-methylxanthine (IBMX) inhibition in rats [7], D-NONOate caused reversible inhibition in rats, 8-bromo-cGMP also inhibited Kv3.2 currents reversibly (inhibition of 30.49 ± 14.8% from control at +20 mV) [13]
Tissue Distribution
Brain
Species:  Mouse
Technique:  Immunohistochemistry
References:  5,19,21
Schwann cells
Species:  Mouse
Technique:  RT-PCR
References:  18
Renshaw cells (spinal interneurons)
Species:  Mouse
Technique:  Immunohistochemistry
References:  19
Brain (fast spiking GABAergic interneurons of the neocortex, hippocampus, caudate, terminal fields of thalamocortical projections, interneurons of the basolateral amygdala, suprachiasmatic nucleus)
Species:  Rat
Technique:  Immunohistochemistry
References:  1,11-12,22
Islets
Species:  Rat
Technique:  Immunocytochemistry
References:  15
Mesenteric artery
Species:  Rat
Technique:  RT-PCR
References:  23
Functional Assays
Electrophysiology study with gene cloning and voltage clamp, using chimeric substitutions to further explore the role of S4 in voltage dependent gating
Species:  Rat
Tissue:  Xenopus laevis Oocytes
Response measured:  Fast activation kinetics
References:  17
Physiological Functions
Important for the high-frequency firing of fast spiking GABAergic interneurons; probably in complex with kv3.1.
Species:  Mouse
Tissue:  Neocortex
References:  2
GABA release via regulation of action potential duration in presynaptic terminals
Species:  Mouse
Tissue:  Cortex
References:  3
Physiological Consequences of Altering Gene Expression
A mouse Kv3.2 knockout model displayed alterations to cortical electroencephagraphic patterns and an increased susceptibility to epileptic seizures consistent with an impairment of a cortical inhibitory mechanism.
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  6
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0005402 abnormal action potential PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0003412 abnormal afterhyperpolarization PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0004994 abnormal brain wave pattern PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0002272 abnormal nervous system electrophysiology PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0001501 abnormal sleep pattern PMID: 12176162 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0001363 increased anxiety-related response PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0000243 myoclonus PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0002064 seizures PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0000951 sporadic seizures PMID: 11124984 
Kcnc2tm1Rudy Kcnc2tm1Rudy/Kcnc2tm1Rudy
B6.129S1-Kcnc2
MGI:96668  MP:0003997 tonic-clonic seizures PMID: 11124984 
Biologically Significant Variants
Type:  Splice variant
Species:  Rat
Description:  Kv3.2 isoform a.
Amino acids:  613
Nucleotide accession: 
Protein accession: 
References:  14
Type:  Splice variant
Species:  Rat
Description:  Kv3.2 isoform b.
Amino acids:  638
Nucleotide accession: 
Protein accession: 
References:  14
Type:  Splice variant
Species:  Human
Description:  Kv3.2 isoform a.
Amino acids:  613
Nucleotide accession: 
Protein accession: 
References:  16
Type:  Splice variant
Species:  Human
Description:  Kv3.2 isoform b.
Amino acids:  638
Nucleotide accession: 
Protein accession: 
References:  16
Type:  Splice variant
Species:  Human
Description:  Kv3.2 isoform c.
Amino acids:  558
Nucleotide accession: 
Protein accession: 
References:  16
Type:  Splice variant
Species:  Human
Description:  Kv3.2 isoform d.
Amino acids:  629
Nucleotide accession: 
Protein accession: 
Type:  Splice variant
Species:  Rat
Description:  Kv3.2 isoform c. partial seq.
Amino acids:  208
Nucleotide accession: 
Protein accession: 
References:  8
Type:  Splice variant
Species:  Mouse
Description:  Kv3.2 isoform b
Amino acids:  642
Nucleotide accession: 
Protein accession: 
References:  20
Type:  Splice variant
Species:  Mouse
Description:  Kv3.2c
Amino acids:  639
Nucleotide accession: 
Protein accession: 
Biologically Significant Variant Comments
Alternative splicing of Kv3 genes is involved in channel localisation [14].

References

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1. Chow A, Erisir A, Farb C, Nadal MS, Ozaita A, Lau D, Welker E, Rudy B. (1999) K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons. J. Neurosci., 19 (21): 9332-45. [PMID:10531438]

2. Erisir A, Lau D, Rudy B, Leonard CS. (1999) Function of specific K(+) channels in sustained high-frequency firing of fast-spiking neocortical interneurons. J. Neurophysiol., 82 (5): 2476-89. [PMID:10561420]

3. Goldberg EM, Watanabe S, Chang SY, Joho RH, Huang ZJ, Leonard CS, Rudy B. (2005) Specific functions of synaptically localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse. J. Neurosci., 25 (21): 5230-5. [PMID:15917463]

4. Haas M, Ward DC, Lee J, Roses AD, Clarke V, D'Eustachio P, Lau D, Vega-Saenz de Miera E, Rudy B. (1993) Localization of Shaw-related K+ channel genes on mouse and human chromosomes. Mamm. Genome, 4 (12): 711-5. [PMID:8111118]

5. Itri JN, Michel S, Vansteensel MJ, Meijer JH, Colwell CS. (2005) Fast delayed rectifier potassium current is required for circadian neural activity. Nat. Neurosci., 8 (5): 650-6. [PMID:15852012]

6. Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B. (2000) Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J. Neurosci., 20 (24): 9071-85. [PMID:11124984]

7. Lien CC, Martina M, Schultz JH, Ehmke H, Jonas P. (2002) Gating, modulation and subunit composition of voltage-gated K(+) channels in dendritic inhibitory interneurones of rat hippocampus. J. Physiol. (Lond.), 538 (Pt 2): 405-19. [PMID:11790809]

8. Luneau C, Wiedmann R, Smith JS, Williams JB. (1991) Shaw-like rat brain potassium channel cDNA's with divergent 3' ends. FEBS Lett., 288 (1-2): 163-7. [PMID:1879548]

9. Madeja M, Müller V, Musshoff U, Speckmann EJ. (2000) Sensitivity of native and cloned hippocampal delayed-rectifier potassium channels to verapamil. Neuropharmacology, 39 (2): 202-10. [PMID:10670415]

10. McCormack T, Vega-Saenz de Miera EC, Rudy B. (1990) Molecular cloning of a member of a third class of Shaker-family K+ channel genes in mammals. Proc. Natl. Acad. Sci. U.S.A., 87 (13): 5227-31. [PMID:2367536]

11. McDonald AJ, Mascagni F. (2006) Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in interneurons of the basolateral amygdala. Neuroscience, 138 (2): 537-47. [PMID:16413129]

12. Moreno H, Kentros C, Bueno E, Weiser M, Hernandez A, Vega-Saenz de Miera E, Ponce A, Thornhill W, Rudy B. (1995) Thalamocortical projections have a K+ channel that is phosphorylated and modulated by cAMP-dependent protein kinase. J. Neurosci., 15 (8): 5486-501. [PMID:7643197]

13. Moreno H, Vega-Saenz de Miera E, Nadal MS, Amarillo Y, Rudy B. (2001) Modulation of Kv3 potassium channels expressed in CHO cells by a nitric oxide-activated phosphatase. J. Physiol. (Lond.), 530 (Pt 3): 345-58. [PMID:11281123]

14. Ponce A, Vega-Saenz de Miera E, Kentros C, Moreno H, Thornhill B, Rudy B. (1997) K+ channel subunit isoforms with divergent carboxy-terminal sequences carry distinct membrane targeting signals. J. Membr. Biol., 159 (2): 149-59. [PMID:9307441]

15. Roe MW, Worley JF, Mittal AA, Kuznetsov A, DasGupta S, Mertz RJ, Witherspoon SM, Blair N, Lancaster ME, McIntyre MS, Shehee WR, Dukes ID, Philipson LH. (1996) Expression and function of pancreatic beta-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J. Biol. Chem., 271 (50): 32241-6. [PMID:8943282]

16. Rudy B, Chow A, Lau D, Amarillo Y, Ozaita A, Saganich M, Moreno H, Nadal MS, Hernandez-Pineda R, Hernandez-Cruz A, Erisir A, Leonard C, Vega-Saenz de Miera E. (1999) Contributions of Kv3 channels to neuronal excitability. Ann. N. Y. Acad. Sci., 868: 304-43. [PMID:10414303]

17. Smith-Maxwell CJ, Ledwell JL, Aldrich RW. (1998) Role of the S4 in cooperativity of voltage-dependent potassium channel activation. J. Gen. Physiol., 111 (3): 399-420. [PMID:9482708]

18. 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]

19. Song ZM, Hu J, Rudy B, Redman SJ. (2006) Developmental changes in the expression of calbindin and potassium-channel subunits Kv3.1b and Kv3.2 in mouse Renshaw cells. Neuroscience, 139 (2): 531-8. [PMID:16460880]

20. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF et al.. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl. Acad. Sci. U.S.A., 99 (26): 16899-903. [PMID:12477932]

21. Tansey EP, Chow A, Rudy B, McBain CJ. (2002) Developmental expression of potassium-channel subunit Kv3.2 within subpopulations of mouse hippocampal inhibitory interneurons. Hippocampus, 12 (2): 137-48. [PMID:12000114]

22. Weiser M, Vega-Saenz de Miera E, Kentros C, Moreno H, Franzen L, Hillman D, Baker H, Rudy B. (1994) Differential expression of Shaw-related K+ channels in the rat central nervous system. J. Neurosci., 14 (3 Pt 1): 949-72. [PMID:8120636]

23. Xu C, Lu Y, Tang G, Wang R. (1999) Expression of voltage-dependent K(+) channel genes in mesenteric artery smooth muscle cells. Am. J. Physiol., 277 (5 Pt 1): G1055-63. [PMID:10564112]

24. Yan L, Herrington J, Goldberg E, Dulski PM, Bugianesi RM, Slaughter RS, Banerjee P, Brochu RM, Priest BT, Kaczorowski GJ, Rudy B, Garcia ML. (2005) Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels. Mol. Pharmacol., 67 (5): 1513-21. [PMID:15709110]

25. Yeung SY, Thompson D, Wang Z, Fedida D, Robertson B. (2005) Modulation of Kv3 subfamily potassium currents by the sea anemone toxin BDS: significance for CNS and biophysical studies. J. Neurosci., 25 (38): 8735-45. [PMID:16177043]

Contributors

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How to cite this page

Jeanne Nerbonne, Bernardo Rudy, K. George Chandy, Stephan Grissmer, George A. Gutman, Michel Lazdunski, David Mckinnon, Luis A. Pardo, Gail A. Robertson, Michael C. Sanguinetti, Walter Stühmer, Xiaoliang Wang.
Voltage-gated potassium channels: Kv3.2. Last modified on 11/09/2015. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=549.