K<SUB>v</SUB>3.4 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Kv3.4

Target id: 551

Nomenclature: Kv3.4

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 Kv3.4 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 635 1p21 KCNC4 potassium voltage-gated channel subfamily C member 4 10-11
Mouse 6 1 628 3 F2.3 Kcnc4 potassium voltage gated channel, Shaw-related subfamily, member 4 11
Rat 6 1 625 2 Kcnc4 potassium voltage-gated channel subfamily C member 4 11
Previous and Unofficial Names
Raw3 | Kcnc4 | potassium voltage-gated channel subfamily C member 4 | Kcr2-4 | potassium voltage gated channel, Shaw-related subfamily, member 4 | potassium voltage-gated channel, Shaw-related subfamily, member 4 | potassium channel, voltage gated Shaw related subfamily C, member 4 | potassium channel, voltage gated Shaw-related subfamily C, member 4 | potassium voltage gated channel
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
MinK-related Peptide 2 1
Other Associated Proteins
Name References
Not determined
Functional Characteristics
KA
Ion Selectivity and Conductance
Species:  Rat
Rank order:  K+ [14.0 pS]
References:  8,11
Species:  Rat
Macroscopic current rectification:  Rapidly activating and inactivating A-Type current
References:  11
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  14.0 - 11 Xenopus laevis oocyte Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -10.0 - 10 Xenopus laevis oocyte Human
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  3.4 - 8 Xenopus laevis oocyte Rat
Inactivation  53.0 16.0 8,10-11
Comments  Fast inactivating
Associated subunits (Human)
MiRP2 is an associated subunit for Kv3.4

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

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
thiopental Rn - 4.0 pIC50 - - 12
pIC50 4.0 [12]
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
sea anemone toxin BDS-I Rn - 7.3 pIC50 - - 3
pIC50 7.3 (IC50 4.7x10-8 M) [3]
DABCO-C16 Rn - 6.2 pIC50 - - 4
pIC50 6.2 [4]
tetraethylammonium Rn - 3.5 pIC50 - - 8,11
pIC50 3.5 (IC50 3x10-4 M) [8,11]
DABCO Rn - 3.2 pIC50 - - 4
pIC50 3.2 [4]
Channel Blocker Comments
The specificity of BDS-I for Kv3.4 has been questioned.
Tissue Distribution
Acinar cells
Species:  Mouse
Technique:  RT-PCR
References:  5-6
Parathyroid, prostate, brain
Species:  Rat
Technique:  RT-PCR
References:  9
Brainstem, hippocampal granule cells, skeletal muscle
Species:  Rat
Technique:  Northern Blot
References:  13
Functional Assays
Whole cell voltage clamp
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  Voltage-gated potassium channel, A-type, fast inactivating
References:  11
Physiological Functions
In combination with MirP2, Kv3.4 forms low-voltage activating potassium channels that regulate skeletal muscle resting potential.
Species:  Rat
Tissue:  Rat skeletal muscle tissue
References:  1
Clinically-Relevant Mutations and Pathophysiology
Disease:  Periodic paralysis
References:  1-2
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human R83H 1-2
Gene Expression and Pathophysiology
Increase in Kv3.4 and MirP2 transcripts and proteins induced after treatment with Aβ1-42
Tissue or cell type:  Hippocampal neurons and PC-12 cells.
Pathophysiology:  Neurodegeneration
Species:  Rat
Technique:  PC-12 cells
References:  7
General Comments
Kv3.4 belongs to the mammalian Shaw-related family.

References

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1. Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA. (2001) MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell, 104 (2): 217-31. [PMID:11207363]

2. Abbott GW, Butler MH, Goldstein SA. (2006) Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. FASEB J., 20 (2): 293-301. [PMID:16449802]

3. Diochot S, Schweitz H, Béress L, Lazdunski M. (1998) Sea anemone peptides with a specific blocking activity against the fast inactivating potassium channel Kv3.4. J. Biol. Chem., 273 (12): 6744-9. [PMID:9506974]

4. Gordon E, Cohen JL, Engel R, Abbott GW. (2006) 1,4-Diazabicyclo[2.2.2]octane derivatives: a novel class of voltage-gated potassium channel blockers. Mol. Pharmacol., 69 (3): 718-26. [PMID:16317109]

5. Göpel SO, Kanno T, Barg S, Rorsman P. (2000) Patch-clamp characterisation of somatostatin-secreting -cells in intact mouse pancreatic islets. J. Physiol. (Lond.), 528 (Pt 3): 497-507. [PMID:11060127]

6. Kalman K, Nguyen A, Tseng-Crank J, Dukes ID, Chandy G, Hustad CM, Copeland NG, Jenkins NA, Mohrenweiser H, Brandriff B, Cahalan M, Gutman GA, Chandy KG. (1998) Genomic organization, chromosomal localization, tissue distribution, and biophysical characterization of a novel mammalian Shaker-related voltage-gated potassium channel, Kv1.7. J. Biol. Chem., 273 (10): 5851-7. [PMID:9488722]

7. Pannaccione A, Boscia F, Scorziello A, Adornetto A, Castaldo P, Sirabella R, Taglialatela M, Di Renzo GF, Annunziato L. (2007) Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death. Mol. Pharmacol., 72 (3): 665-73. [PMID:17495071]

8. Rettig J, Wunder F, Stocker M, Lichtinghagen R, Mastiaux F, Beckh S, Kues W, Pedarzani P, Schröter KH, Ruppersberg JP. (1992) Characterization of a Shaw-related potassium channel family in rat brain. EMBO J., 11 (7): 2473-86. [PMID:1378392]

9. Riazanski V, Becker A, Chen J, Sochivko D, Lie A, Wiestler OD, Elger CE, Beck H. (2001) Functional and molecular analysis of transient voltage-dependent K+ currents in rat hippocampal granule cells. J. Physiol. (Lond.), 537 (Pt 2): 391-406. [PMID:11731573]

10. Rudy B, Sen K, Vega-Saenz de Miera E, Lau D, Ried T, Ward DC. (1991) Cloning of a human cDNA expressing a high voltage-activating, TEA-sensitive, type-A K+ channel which maps to chromosome 1 band p21. J. Neurosci. Res., 29 (3): 401-12. [PMID:1920536]

11. Schröter KH, Ruppersberg JP, Wunder F, Rettig J, Stocker M, Pongs O. (1991) Cloning and functional expression of a TEA-sensitive A-type potassium channel from rat brain. FEBS Lett., 278 (2): 211-6. [PMID:1840526]

12. Suzuki H, Momoi N, Ono T, Maeda S, Shikama Y, Matsuoka I, Suzuki H, Kimura J. (2005) Inhibitory effect of thiopental on ultra-rapid delayed rectifier K+ current in H9c2 cells. J. Pharmacol. Sci., 99 (2): 177-84. [PMID:16217144]

13. 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]

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: Kv3.4. Last modified on 15/09/2015. Accessed on 12/12/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=551.