K<SUB>v</SUB>3.3 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

Kv3.3

Target id: 550

Nomenclature: Kv3.3

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 Kv3.3 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 757 19q13.3-13.4 KCNC3 potassium voltage-gated channel subfamily C member 3 3,15
Mouse 6 1 769 7 B4 Kcnc3 potassium voltage gated channel, Shaw-related subfamily, member 3 15
Rat 6 1 769 1q22 Kcnc3 potassium voltage-gated channel subfamily C member 3
Previous and Unofficial Names
potassium voltage-gated channel subfamily C member 3 | Kcr2-3 | potassium voltage gated channel, Shaw-related subfamily, member 3 | potassium voltage-gated channel, Shaw-related subfamily, member 3 | potassium channel, voltage gated Shaw related subfamily C, member 3 | potassium channel, voltage gated Shaw-related subfamily C, member 3 | potassium voltage gated channel
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
KA
Ion Selectivity and Conductance
Species:  Rat
Macroscopic current rectification:  Rapidly activating, delayed rectifier
References:  23
Ion Selectivity and Conductance Comments
K+ ion selectivity; details not established
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  7.0 - 23 Xenopus laevis oocyte Rat
Inactivation  - 200.0 23
Voltage Dependence Comments
Also carried out in CHO and HEK293 cells transfected with the teleost homologue of Kv3.3 known as AptKv3.3 [10]

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
tetraethylammonium Rn - 3.9 pIC50 - - 23
pIC50 3.9 (IC50 1.4x10-4 M) [23]
fampridine Rn - 2.9 pIC50 - - 23
pIC50 2.9 [23]
Tissue Distribution
Myocardium
Species:  Human
Technique:  RT-PCR
References:  19
Brain (auditory nuclei, cerebellar Purkinje cells)
Species:  Mouse
Technique:  Immunohistochemistry
References:  4-5,14,22
Medulla oblongata and spinal cord
Species:  Rat
Technique:  Immunohistochemistry
References:  3
Brain (brainstem and cerebellum > forebrain), axons, terminals, somas and distal dendrites, Purkinje cells, central nervous system motorneurons, auditory brainstem, mesenteric artery.
Species:  Rat
Technique:  Immunohistochemistry
References:  1,25
Tissue Distribution Comments
Also detected in rabbit lens and corneal epithelium [21]
Functional Assays
Voltage clamp
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  Voltage-gated A-type potassium channel
References:  23
Physiological Functions
Controls the rate of spontaneous action potential firing of Purkinje neurons and regulates the dynamics of synaptic transmission.
Species:  Mouse
Tissue:  Cerebellum, Purkinje cells.
References:  2,16-18,26-27
Involved in motor control, such as cortex, basal ganglia and cerrebellum.
Species:  Mouse
Tissue:  Brain
References:  16-18,26-27
Physiological Consequences of Altering Gene Expression
Mice lacking Kv3.3 alone or Kv3.3 and Kv3.1 display impaired motor coordination, behavioural deficits and alcohol sensitivity.
Species:  Mouse
Tissue: 
Technique:  Knockout
References:  5-9,18
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001393 ataxia PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001265 decreased body size PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0005534 decreased body temperature PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001262 decreased body weight PMID: 11517255 
Kcnc1+|Kcnc1tm1Joho|Kcnc3+|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1+,Kcnc3tm1Echa/Kcnc3+
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001262 decreased body weight PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0009751 enhanced behavioral response to alcohol PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001399 hyperactivity PMID: 11517255 
Kcnc1+|Kcnc1tm1Joho|Kcnc3+|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1+,Kcnc3tm1Echa/Kcnc3+
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001399 hyperactivity PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001525 impaired balance PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001405 impaired coordination PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001415 increased exploration in new environment PMID: 11517255 
Kcnc1+|Kcnc1tm1Joho|Kcnc3+|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1+,Kcnc3tm1Echa/Kcnc3+
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001415 increased exploration in new environment PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0005424 jerky movement PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0008569 lethality at weaning PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0000243 myoclonus PMID: 11517255 
Kcnc3tm1Echa Kcnc3tm1Echa/Kcnc3tm1Echa
Not Specified
MGI:96669  MP:0002169 no abnormal phenotype detected PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0008489 postnatal slow weight gain PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0000745 tremors PMID: 11517255 
Kcnc1tm1Joho|Kcnc3tm1Echa Kcnc1tm1Joho/Kcnc1tm1Joho,Kcnc3tm1Echa/Kcnc3tm1Echa
involves: 129/Sv * C57BL/6
MGI:96667  MGI:96669  MP:0001263 weight loss PMID: 11517255 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Spinocerebellar ataxia 13; SCA13
Synonyms: Spinocerebellar ataxia [Disease Ontology: DOID:1441]
Disease Ontology: DOID:1441
OMIM: 605259
Orphanet: ORPHA98768
Role: 
References:  6,11-13,20,24
General Comments
Mice lacking Kv3.3 and Kv3.1 show alcohol hypersensitivity, increased locomotion and myoclonus [8]
It is a member of the mammalian Shaw-related family.

References

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1. Adelman JP, Bond CT, Pessia M, Maylie J. (1995) Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron, 15 (6): 1449-54. [PMID:8845167]

2. Akemann W, Knöpfel T. (2006) Interaction of Kv3 potassium channels and resurgent sodium current influences the rate of spontaneous firing of Purkinje neurons. J. Neurosci., 26 (17): 4602-12. [PMID:16641240]

3. Brooke RE, Atkinson L, Edwards I, Parson SH, Deuchars J. (2006) Immunohistochemical localisation of the voltage gated potassium ion channel subunit Kv3.3 in the rat medulla oblongata and thoracic spinal cord. Brain Res., 1070 (1): 101-15. [PMID:16403474]

4. Brooke RE, Corns L, Edwards IJ, Deuchars J. (2010) Kv3.3 immunoreactivity in the vestibular nuclear complex of the rat with focus on the medial vestibular nucleus: targeting of Kv3.3 neurones by terminals positive for vesicular glutamate transporter 1. Brain Res., 1345: 45-58. [PMID:20471378]

5. Chang SY, Zagha E, Kwon ES, Ozaita A, Bobik M, Martone ME, Ellisman MH, Heintz N, Rudy B. (2007) Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations of mouse brain. J. Comp. Neurol., 502 (6): 953-72. [PMID:17444489]

6. Duarri A, Nibbeling EA, Fokkens MR, Meijer M, Boerrigter M, Verschuuren-Bemelmans CC, Kremer BP, van de Warrenburg BP, Dooijes D, Boddeke E et al.. (2015) Functional analysis helps to define KCNC3 mutational spectrum in dutch ataxia cases. PLoS ONE, 10 (3): e0116599. [PMID:25756792]

7. Espinosa F, Marks G, Heintz N, Joho RH. (2004) Increased motor drive and sleep loss in mice lacking Kv3-type potassium channels. Genes Brain Behav., 3 (2): 90-100. [PMID:15005717]

8. Espinosa F, McMahon A, Chan E, Wang S, Ho CS, Heintz N, Joho RH. (2001) Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J. Neurosci., 21 (17): 6657-65. [PMID:11517255]

9. Espinosa F, Torres-Vega MA, Marks GA, Joho RH. (2008) Ablation of Kv3.1 and Kv3.3 potassium channels disrupts thalamocortical oscillations in vitro and in vivo. J. Neurosci., 28 (21): 5570-81. [PMID:18495891]

10. Fernandez FR, Morales E, Rashid AJ, Dunn RJ, Turner RW. (2003) Inactivation of Kv3.3 potassium channels in heterologous expression systems. J. Biol. Chem., 278 (42): 40890-8. [PMID:12923191]

11. Figueroa KP, Minassian NA, Stevanin G, Waters M, Garibyan V, Forlani S, Strzelczyk A, Bürk K, Brice A, Dürr A et al.. (2010) KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients. Hum. Mutat., 31 (2): 191-6. [PMID:19953606]

12. Figueroa KP, Waters MF, Garibyan V, Bird TD, Gomez CM, Ranum LP, Minassian NA, Papazian DM, Pulst SM. (2011) Frequency of KCNC3 DNA variants as causes of spinocerebellar ataxia 13 (SCA13). PLoS ONE, 6 (3): e17811. [PMID:21479265]

13. Ghanshani S, Pak M, McPherson JD, Strong M, Dethlefs B, Wasmuth JJ, Salkoff L, Gutman GA, Chandy KG. (1992) Genomic organization, nucleotide sequence, and cellular distribution of a Shaw-related potassium channel gene, Kv3.3, and mapping of Kv3.3 and Kv3.4 to human chromosomes 19 and 1. Genomics, 12 (2): 190-6. [PMID:1740329]

14. Grigg JJ, Brew HM, Tempel BL. (2000) Differential expression of voltage-gated potassium channel genes in auditory nuclei of the mouse brainstem. Hear. Res., 140 (1-2): 77-90. [PMID:10675636]

15. 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]

16. Hurlock EC, Bose M, Pierce G, Joho RH. (2009) Rescue of motor coordination by Purkinje cell-targeted restoration of Kv3.3 channels in Kcnc3-null mice requires Kcnc1. J. Neurosci., 29 (50): 15735-44. [PMID:20016089]

17. Hurlock EC, McMahon A, Joho RH. (2008) Purkinje-cell-restricted restoration of Kv3.3 function restores complex spikes and rescues motor coordination in Kcnc3 mutants. J. Neurosci., 28 (18): 4640-8. [PMID:18448641]

18. Joho RH, Street C, Matsushita S, Knöpfel T. (2006) Behavioral motor dysfunction in Kv3-type potassium channel-deficient mice. Genes Brain Behav., 5 (6): 472-82. [PMID:16923152]

19. Ordög B, Brutyó E, Puskás LG, Papp JG, Varró A, Szabad J, Boldogkoi Z. (2006) Gene expression profiling of human cardiac potassium and sodium channels. Int. J. Cardiol., 111 (3): 386-93. [PMID:16257073]

20. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Dolan CR, Fong CT, Smith RJH et al.. (1993) Spinocerebellar Ataxia Type 13. GeneReviews(®),. [PMID:20301404]

21. Rae JL, Shepard AR. (2000) Kv3.3 potassium channels in lens epithelium and corneal endothelium. Exp. Eye Res., 70 (3): 339-48. [PMID:10712820]

22. Sacco T, De Luca A, Tempia F. (2006) Properties and expression of Kv3 channels in cerebellar Purkinje cells. Mol. Cell. Neurosci., 33 (2): 170-9. [PMID:16949837]

23. Vega-Saenz de Miera E, Moreno H, Fruhling D, Kentros C, Rudy B. (1992) Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel. Proc. Biol. Sci., 248 (1321): 9-18. [PMID:1381835]

24. Waters MF, Minassian NA, Stevanin G, Figueroa KP, Bannister JP, Nolte D, Mock AF, Evidente VG, Fee DB, Müller U et al.. (2006) Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat. Genet., 38 (4): 447-51. [PMID:16501573]

25. 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]

26. Zagha E, Lang EJ, Rudy B. (2008) Kv3.3 channels at the Purkinje cell soma are necessary for generation of the classical complex spike waveform. J. Neurosci., 28 (6): 1291-300. [PMID:18256249]

27. Zagha E, Manita S, Ross WN, Rudy B. (2010) Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes. J. Neurophysiol., 103 (6): 3516-25. [PMID:20357073]

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: Kv3.3. Last modified on 15/09/2015. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=550.