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Kv3.2

Family: Voltage-gated potassium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Ion Selectivity and Conductance
Voltage Dependence
Gating Inhibitors
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
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, Shaw-related subfamily, 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, Shaw-related subfamily, member 2
Previous and Unofficial Names
RKShIIIA
Raw1
kv3.2a
rkv3.2b
rkv3.2c
AW047325
B230117I07
Kv3.2
KShIIIA
potassium voltage gated channel, Shaw-related subfamily, member 2
potassium voltage-gated channel subfamily C member 2
voltage-gated potassium channel subunit Kv3.2
Database Links
Ensembl ENSG00000166006 (Hs), ENSMUSG00000035681 (Mm), ENSRNOG00000004077 (Rn)
Entrez Gene 3747 (Hs), 268345 (Mm), 246153 (Rn)
GeneCards KCNC2 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcnc2 (Mm)
HomoloGene 71199 (Hs)
Human Protein Reference Database 08883 (Hs)
InterPro Q96PR1 (Hs), Q14B80 (Mm), P22462 (Rn)
KEGG Gene hsa:3747 (Hs), mmu:268345 (Mm), rno:246153 (Rn)
OMIM 176256 (Hs)
PharmGKB Gene PA35490 (Hs)
PhosphoSitePlus Q96PR1 (Hs), Q14B80 (Mm)
Protein Ontology (PRO) PRO:000000782 (Hs)
RefSeq Nucleotide NM_139136 (Hs), NM_153748 (Hs), NM_139137 (Hs), NM_001025581 (Mm), NM_139217 (Rn), NM_139216 (Rn)
RefSeq Protein NP_631874 (Hs), NP_631875 (Hs), NP_715624 (Hs), NP_001020752 (Mm), NP_631962 (Rn), NP_631963 (Rn)
TreeFam ENSG00000166006 (Hs), ENSMUSG00000035681 (Mm), ENSRNOG00000004077 (Rn)
UniGene Hs. 27214 (Hs)
UniProt Q96PR1 (Hs), Q14B80 (Mm), P22462 (Rn)
Wikipedia Kv3.2
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated potassium channels Kv3.2 Search by accession number: Q96PR1, Q14B80, P22462
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.
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]
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
verapamil Rn 4.9 pEC50 - - 9
4-aminopyridine Rn 4.6 pEC50 - - 7
tetraethylammonium Rn 4.2 pEC50 - - 7
ShK Toxin Hs 9.5 pIC50 - - 24
View species-specific pore blocker tables
Pore 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:  Relatively 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
Not Determined
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

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 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alterations to cortical electroencephagraphic patterns and an increased susceptibility to epileptic seizures consistent with an impairment of a cortical inhibitory mechanism.
References:  6
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Mouse Kv3.2 knock-out 6
Gene Expression and Pathophysiology
Not Determined
Biologically Significant Variants
Kv3.2 isoform d.
Nucleotide accession:  AY243473 
Protein accession:  AAO89503 
Amino acids:  629
Type:  Splice variant
Species:  Human
References: 
Kv3.2 isoform c. partial seq.
Nucleotide accession:  M59313 
Protein accession:  AAA41820 
Amino acids:  208
Type:  Splice variant
Species:  Rat
References:  8
Kv3.2 isoform b
Nucleotide accession:  BC116290 
Protein accession:  AAI16291 
Amino acids:  642
Type:  Splice variant
Species:  Mouse
References:  20
Kv3.2c
Nucleotide accession:  NM_001025581 
Protein accession:  NP_001020752 
Amino acids:  639
Type:  Splice variant
Species:  Mouse
References: 
Kv3.2 isoform a.
Nucleotide accession:  NM_139216 
Protein accession:  NP_631962 
Amino acids:  613
Type:  Splice variant
Species:  Rat
References:  14
Kv3.2 isoform b.
Nucleotide accession:  NM_139217 
Protein accession:  NP_631963 
Amino acids:  638
Type:  Splice variant
Species:  Rat
References:  14
Kv3.2 isoform a.
Nucleotide accession:  NM_139136 
Protein accession:  NP_631874 
Amino acids:  613
Type:  Splice variant
Species:  Human
References:  16
Kv3.2 isoform b.
Nucleotide accession:  NM_139137 
Protein accession:  NP_631875 
Amino acids:  638
Type:  Splice variant
Species:  Human
References:  16
Kv3.2 isoform c.
Nucleotide accession:  NM_153748 
Protein accession:  NP_715624 
Amino acids:  558
Type:  Splice variant
Species:  Human
References:  16
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, R. L., Feingold, E. A., Grouse, L. H., Derge, J. G. 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: 16899-16903. [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. , 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]

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: Kv3.2. Last modified on 01/07/2010. Accessed on 26/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=549.


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