Nomenclature: Kv3.1

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 511 11p15 KCNC1 potassium voltage-gated channel, Shaw-related subfamily, member 1
Mouse 6 1 511 7 B4 Kcnc1 potassium voltage gated channel, Shaw-related subfamily, member 1
Rat 6 1 585 1q22 Kcnc1 potassium voltage gated channel, Shaw-related subfamily, member 1 21
Previous and Unofficial Names
Kv3.1
NGK2
KV4
KShIIIB
Raw2
C230009H10Rik
Kcr2-1
Shaw
MGC129855
NGK2-KV4
potassium channel gene 1
potassium voltage gated channel, Shaw-related subfamily, member 1
potassium voltage-gated channel subfamily C member 1
voltage-gated potassium channel subunit Kv3.1
voltage-gated potassium channel subunit Kv4
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Functional Characteristics
KV
Ion Selectivity and Conductance
Species:  Mouse
Rank order:  K+ [27.0 pS] > Rb+ [25.0 pS] > Cs+ [2.7 pS] = NH4+ [2.7 pS] > Na+ [0.1 pS]
References:  3-4,7,27-28
Species:  Mouse
Macroscopic current rectification:  Delayed Rectifier Current
References:  3,27
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  16.0 - 8 L929 Mouse
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  - - Xenopus laevis Oocytes Rat
Inactivation  - 9800.0 18
Comments  U-type inactivation also makes a major but previously unrecognised contribution to slow inactivation of Shaker [18]
Gating inhibitors
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
fluoxetine Rn - 6.1 pIC50 - - 1
pIC50 6.1 [1]
norfluoxetine Rn - 4.9 pIC50 - - 1
pIC50 4.9 [1]
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
fampridine Mm - 4.5 pIC50 - - 8
pIC50 4.5 [8]
resiniferatoxin Mm - 4.3 pIC50 - - 8
pIC50 4.3 [8]
flecainide Mm - 4.0 pIC50 - - 8
pIC50 4.0 [8]
diltiazem Mm - 4.0 pIC50 - - 8
pIC50 4.0 [8]
nifedipine Mm - 3.9 pIC50 - - 8
pIC50 3.9 [8]
capsaicin Mm - 3.8 pIC50 - - 8
pIC50 3.8 [8]
tetraethylammonium Mm - 3.7 pIC50 - - 8
pIC50 3.7 [8]
cromakalim Mm - 3.6 pIC50 - - 8
pIC50 3.6 [8]
Tissue Distribution
SH-SY5Y cell line, human Louckes B cells
Species:  Human
Technique:  RT-PCR
References:  25
Anterior pituitary cells (AtT20)
Species:  Mouse
Technique:  In situ hybridisation, RT-PCR
References:  9,22
Brain (MNTB neurons > dorsal cochlear nucleus (DCN), ventral posterior cochlear nucleus (VCP), cerebellum, granule cells, Purkinje cells
Species:  Mouse
Technique:  In situ hybridisation
References:  31
Mouse Lung Fibroblasts (MLF)
Species:  Mouse
Technique:  Electrophysiology
References:  29
Testis, germ cell, pancreatic islets alpha cells
Species:  Mouse
Technique:  RT-PCR
References:  6
Skeletal muscle
Species:  Rat
Technique:  In situ hybridisation, northern blot
References:  33
Brain (cerebellum > globus pallidus, subthalamic nucleus, substantia nigra > reticular thalamic nuclei, cortical and hippocampal interneurons > inferior colliculi, cochlear and vestibular nuclei, nucleus tractus solitarii, striatal GABA-ergic neurons)
Species:  Rat
Technique:  Immunohistochemistry
References:  2,15,19,32
Functional Assays
Gene cloning and voltage clamp
Species:  Human
Tissue:  NIH 3T3 fibroblasts
Response measured:  Threshold of activation at approximately -10mV, showed little inactivation. It is sensitive to blockade by 4-AP and TEA, and appears to have two gating behaviours.
References:  16-17
Physiological Functions
Important for the high-firing frequency of neurons
Species:  Rat
Tissue:  Cortical neurons, globus pallidus
References:  10,22
Fast-spiking GABAergic interneurons
Species:  Mouse
Tissue:  AtT20 cells (anterior pituitary derived)
References:  9
Regulation of action potential duration in presynaptic terminals
Species:  Rat
Tissue:  Presynaptic terminals
References:  12,23,26
Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock-like mechanisms
Species:  Mouse
Tissue:  Brain
References:  13
Physiological Consequences of Altering Gene Expression
Kv3.1 knock-out mice displayed constitutively increased locomotor activity and sleep loss
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  11
Kv3.1 knock-out mice displayed impaired motor skills and reduced muscle contraction force
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  14
Kv3.1/ Kv3.3 double knock-out mice displayed a phenotype of severe ataxia, myoclonus and hypersensitivity to ethanol
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  5
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

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 
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 
Gene Expression and Pathophysiology
mRNA expression increased in colonic carcinoma
Tissue or cell type:  Colonic cancer cells
Pathophysiology:  Colonic carcinoma
Species:  Human
Technique: 
References:  24
mRNA expression increased in colonic carcinoma
Tissue or cell type:  Colonic cancer cells
Pathophysiology:  Colonic carcinoma
Species:  Mouse
Technique: 
References:  24
Inhibition of Kv3.1 channel gene expression by chronic hypoxia
Tissue or cell type:  Distal pulmonary artery
Pathophysiology:  Chronic hypoxia
Species:  Rat
Technique: 
References:  30
Biologically Significant Variants
Type:  Splice variant
Species:  Mouse
Description:  Kv3.1a mRNA levels may be modulated by neuronal activity.
Amino acids:  585
Nucleotide accession: 
Protein accession: 
References:  20,34
Type:  Splice variant
Species:  Rat
Description:  The Kv3.1b subunit in the soma of some interneuronal populations may support their ability to fire trains of short duration action potentials at very high rate by facilitating the recovery of Na+ channel inactivation and minimizing the duration of the afterhyperpolarization.
Amino acids:  638
Nucleotide accession: 
Protein accession: 
References:  2
Biologically Significant Variant Comments
Kv3.1b isoform is the most abundant and thus is the most studied isoform.
General Comments
H-ras oncogene switches anterior pituitary derived cells (AtT20) to a more neuron-like phenotype in parallel with the induction of expression of Kv3.112. It is a member of the mammalian Shaw-related family.

REFERENCES

1. Choi BH, Choi JS, Yoon SH, Rhie DJ, Min DS, Jo YH, Kim MS, Hahn SJ. (2001) Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1. Neuropharmacology41 (4): 443-53. [PMID:11543764]

2. Dallas ML, Atkinson L, Milligan CJ, Morris NP, Lewis DI, Deuchars SA, Deuchars J. (2005) Localization and function of the Kv3.1b subunit in the rat medulla oblongata: focus on the nucleus tractus solitarii. J. Physiol. (Lond.)562 (Pt 3): 655-72. [PMID:15528247]

3. De Biasi M, Drewe JA, Kirsch GE, Brown AM. (1993) Histidine substitution identifies a surface position and confers Cs+ selectivity on a K+ pore. Biophys. J.65 (3): 1235-42. [PMID:8241404]

4. DeCoursey TE, Chandy KG, Gupta S, Cahalan MD. (1984) Voltage-gated K+ channels in human T lymphocytes: a role in mitogenesis?. Nature307 (5950): 465-8. [PMID:6320007]

5. 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]

6. Felix R, Serrano CJ, Treviño CL, Muñoz-Garay C, Bravo A, Navarro A, Pacheco J, Tsutsumi V, Darszon A. (2002) Identification of distinct K+ channels in mouse spermatogenic cells and sperm. Zygote10 (2): 183-8. [PMID:12056459]

7. Grissmer S, Ghanshani S, Dethlefs B, McPherson JD, Wasmuth JJ, Gutman GA, Cahalan MD, Chandy KG. (1992) The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes the type l K+ channel in T cells. J. Biol. Chem.267 (29): 20971-9. [PMID:1400413]

8. 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]

9. Hemmick LM, Perney TM, Flamm RE, Kaczmarek LK, Birnberg NC. (1992) Expression of the H-ras oncogene induces potassium conductance and neuron-specific potassium channel mRNAs in the AtT20 cell line. J. Neurosci.12 (6): 2007-14. [PMID:1607925]

10. Hernández-Pineda R, Chow A, Amarillo Y, Moreno H, Saganich M, Vega-Saenz de Miera EC, Hernández-Cruz A, Rudy B. (1999) Kv3.1-Kv3.2 channels underlie a high-voltage-activating component of the delayed rectifier K+ current in projecting neurons from the globus pallidus. J. Neurophysiol.82 (3): 1512-28. [PMID:10482766]

11. Ho CS, Grange RW, Joho RH. (1997) Pleiotropic effects of a disrupted K+ channel gene: reduced body weight, impaired motor skill and muscle contraction, but no seizures. Proc. Natl. Acad. Sci. U.S.A.94 (4): 1533-8. [PMID:9037088]

12. Ishikawa T, Nakamura Y, Saitoh N, Li WB, Iwasaki S, Takahashi T. (2003) Distinct roles of Kv1 and Kv3 potassium channels at the calyx of Held presynaptic terminal. J. Neurosci.23 (32): 10445-53. [PMID:14614103]

13. Joho RH, Marks GA, Espinosa F. (2006) Kv3 potassium channels control the duration of different arousal states by distinct stochastic and clock-like mechanisms. Eur. J. Neurosci.23 (6): 1567-74. [PMID:16553620]

14. 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]

15. Jung DK, Lee SY, Kim D, Joo KM, Cha CI, Yang HS, Lee WB, Chung YH. (2005) Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear nuclei. Neurol. Res.27 (4): 436-40. [PMID:15949244]

16. Kanemasa T, Gan L, Perney TM, Wang LY, Kaczmarek LK. (1995) Electrophysiological and pharmacological characterization of a mammalian Shaw channel expressed in NIH 3T3 fibroblasts. J. Neurophysiol.74 (1): 207-17. [PMID:7472324]

17. Kirsch GE, Drewe JA. (1993) Gating-dependent mechanism of 4-aminopyridine block in two related potassium channels. J. Gen. Physiol.102 (5): 797-816. [PMID:8301258]

18. Klemic KG, Kirsch GE, Jones SW. (2001) U-type inactivation of Kv3.1 and Shaker potassium channels. Biophys. J.81 (2): 814-26. [PMID:11463627]

19. Lenz S, Perney TM, Qin Y, Robbins E, Chesselet MF. (1994) GABA-ergic interneurons of the striatum express the Shaw-like potassium channel Kv3.1. Synapse18 (1): 55-66. [PMID:7825124]

20. Liu SJ, Kaczmarek LK. (1998) The expression of two splice variants of the Kv3.1 potassium channel gene is regulated by different signaling pathways. J. Neurosci.18 (8): 2881-90. [PMID:9526005]

21. Luneau CJ, Williams JB, Marshall J, Levitan ES, Oliva C, Smith JS, Antanavage J, Folander K, Stein RB, Swanson R. (1991) Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system. Proc. Natl. Acad. Sci. U.S.A.88 (9): 3932-6. [PMID:2023941]

22. Massengill JL, Smith MA, Son DI, O'Dowd DK. (1997) Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes. J. Neurosci.17 (9): 3136-47. [PMID:9096148]

23. McKay BE, Turner RW. (2004) Kv3 K+ channels enable burst output in rat cerebellar Purkinje cells. Eur. J. Neurosci.20 (3): 729-39. [PMID:15255983]

24. Ousingsawat J, Spitzner M, Puntheeranurak S, Terracciano L, Tornillo L, Bubendorf L, Kunzelmann K, Schreiber R. (2007) Expression of voltage-gated potassium channels in human and mouse colonic carcinoma. Clin. Cancer Res.13 (3): 824-31. [PMID:17289873]

25. Plant LD, Boyle JP, Thomas NM, Hipkins NJ, Benedikz E, Hooper NM, Henderson Z, Vaughan PF, Peers C, Cowburn RF, Pearson HA. (2002) Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH-SY5Y. Neuroreport13 (12): 1553-6. [PMID:12218704]

26. 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]

27. Shapiro MS, DeCoursey TE. (1991) Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes. J. Gen. Physiol.97 (6): 1251-78. [PMID:1875189]

28. Shapiro MS, DeCoursey TE. (1991) Selectivity and gating of the type L potassium channel in mouse lymphocytes. J. Gen. Physiol.97 (6): 1227-50. [PMID:1875188]

29. Shumilina E, Lampert A, Lupescu A, Myssina S, Strutz-Seebohm N, Henke G, Grahammer F, Wulff P, Kuhl D, Lang F. (2005) Deranged Kv channel regulation in fibroblasts from mice lacking the serum and glucocorticoid inducible kinase SGK1. J. Cell. Physiol.204 (1): 87-98. [PMID:15605386]

30. Wang J, Weigand L, Wang W, Sylvester JT, Shimoda LA. (2005) Chronic hypoxia inhibits Kv channel gene expression in rat distal pulmonary artery. Am. J. Physiol. Lung Cell Mol. Physiol.288 (6): L1049-58. [PMID:15665041]

31. Wang LY, Gan L, Forsythe ID, Kaczmarek LK. (1998) Contribution of the Kv3.1 potassium channel to high-frequency firing in mouse auditory neurones. J. Physiol. (Lond.)509 ( Pt 1): 183-94. [PMID:9547392]

32. Weiser M, Bueno E, Sekirnjak C, Martone ME, Baker H, Hillman D, Chen S, Thornhill W, Ellisman M, Rudy B. (1995) The potassium channel subunit KV3.1b is localized to somatic and axonal membranes of specific populations of CNS neurons. J. Neurosci.15 (6): 4298-314. [PMID:7790912]

33. 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]

34. Yokoyama S, Imoto K, Kawamura T, Higashida H, Iwabe N, Miyata T, Numa S. (1989) Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells. Primary structure and functional expression from cDNAs. FEBS Lett.259 (1): 37-42. [PMID:2599109]

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: Kv3.1. Last modified on 29/11/2013. Accessed on 24/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=548.

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