Nomenclature: Kv1.3

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 0 575 1p13.3 KCNA3 potassium voltage-gated channel, shaker-related subfamily, member 3 2,20,24
Mouse 6 0 528 3 F2.3 Kcna3 potassium voltage-gated channel, shaker-related subfamily, member 3 10
Rat 6 0 525 2q34 Kcna3 potassium voltage-gated channel, shaker-related subfamily, member 3 16,59
Previous and Unofficial Names
MK3
MBK3
RCK3
hPCN3
HuK (III)
HLK3
RGK5
KV3
HGK5
n-channel
Kv1.3
potassium voltage gated channel, shaker related subfamily, member 3
potassium voltage-gated channel subfamily A member 3
potassium voltage-gated channel, shaker-related subfamily, member 3
voltage-gated potassium channel subunit Kv1.3
voltage-gated potassium channel subunit Kv3
Mk-3
Kca1-3
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
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kvβ2 6,44
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
SAP97 6,27
β1 integrin 6,36
ZIP 6
Functional Characteristics
KV
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [18.0 - 9.0 (median: 13.0) pS] > Rb+ [10.0 pS] > NH4+ [1.3 pS] > Cs+ [0.26 pS]
References:  8
Species:  Human
Macroscopic current rectification:  Delayed Rectifier K+ current
References:  8
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -33.0 2.6 6 T cells Rat
Inactivation  - -
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -14.1 - 16 T cells Rat
Inactivation  -33.0 612.0 16
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -30.0 - 24-25 Xenopus laevis oocyte Mouse
Inactivation  - 55.0 – 250.0 24
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -25.0 - 58 L929 Rat
Inactivation  -44.0 - 58
Associated subunits (Human)
Kv β1 and Kv β2
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
charybdotoxin Hs - 7.5 – 9.7 (median: 8.7) pKd - - 2,23,52
pKd 7.5 – 9.7 (median: 8.7) [2,23,52]
charybdotoxin Rn - 8.6 pKd - - 25
pKd 8.6 [25]
5-(4-phenoxybutoxy)psoralen Mm - 8.7 pEC50 - - 55
pEC50 8.7 [55]
OSK1-K16-D20 Mm - 11.5 pIC50 - - 47
pIC50 11.5 [47]
ShK Toxin Rn - 12.0 – 9.9 (median: 11.0) pIC50 - - 31,46,50
pIC50 12.0 – 9.9 (median: 11.0) [31,46,50]
ShK(L5) Rn - 10.2 – 10.9 pIC50 - - 4
pIC50 10.2 – 10.9 [4]
margatoxin Hs - 10.3 – 10.0 pIC50 - - 22-23
pIC50 10.3 – 10.0 [22-23]
kaliotoxin Rn - 9.2 pIC50 - - 25
pIC50 9.2 [25]
correolide Hs - 7.1 pIC50 - - 19
pIC50 7.1 (IC50 8.6x10-8 M) [19]
View species-specific channel blocker tables
Channel Blocker Comments
No differences in activity of blockers reported between mouse, rat and human Kv1.3.

Kv1.3 is blocked by a large number of other scorpion and sea anemone toxins including HsTX1 (12 ρM), OSK1 (14 ρM), Pi2 (50 ρM), ShK-Dap22 (23 - 110 ρM), agiotoxin-2 (200 ρM), and BgK (39ηM). (Data in brackets are IC50 values). This is in addition to the classical K+ channel blockers such as 4-AP (195 μM), TEA (10 mM) and the small molecules Psora-4 (3 ηM), PAC (149 ηM), UK-78282 (200 ηM), and verapamil (6 μM). For extensive reviews of these and other blockers, see [9,11].
Tissue Distribution
T- and B- lymphocytes, alveolar macrophages, monocyte derived macrophages, prostate epithelium, platelets, cerebral cortical grey matter
Species:  Human
Technique:  Immunohistochemistry, RT-PCR, Electrophysiology, RNA : GNF / SymAtlas
References:  6,13-14,39,41-42,48,66
Olfactory bulb, peritoneal and bone marrow derived macrophages, osteoclasts
Species:  Mouse
Technique:  Northern Blot, Immunohistochemistry, Electrophysiology
References:  1,18,63,68
Brain synaptic membranes, olfactory bulb, hippocampal microglia, cultured microglia, osteoclasts, cultured oligodendrocyte progenitor cells, platelets, choroid plexus, testis
Species:  Rat
Technique:  Immunohistochemistry, Northern Blot, RT-PCR, Electrophysiology
References:  1,12,17,21,29-30,32,35,42,56
Kidney and colon epithelia
Species:  Rabbit
Technique:  Immunohistochemistry
References:  26
Tissue Distribution Comments
Two mouse knock-out studies report effects on adipocytes [38,67].
Functional Assays
86 Rb+ flux in CHO cells expressing Kv1.3 / T-lymphocytes
Species:  Human
Tissue:  CHO cells / T-lymphocytes
Response measured:  Rb+ efflux following depolarisation with high K+
References:  29
Patch clamp of T-lymphocytes
Species:  Mouse
Tissue:  Isolated T-cells
Response measured:  K+ current by patch clamp
References:  24,37,40
Patch clamp of T-lymphocytes
Species:  Rat
Tissue:  Isolated T-cells
Response measured:  K+ current by patch clamp
References:  5
Patch clamp of T-lymphocytes
Species:  Human
Tissue:  Isolated T-cells
Response measured:  K+ current by patch clamp
References:  2,6,8,14,20,36,65
125I-charybdotoxin or 125I-HgTX1 (A19Y / Y37F) binding assay
Species:  Human
Tissue:  T-lymphocytes
Response measured:  Displacement of 125I-charybdotoxin or 125I-HgTX1 (A19Y / Y37F)
References:  45,49,53
Kv1.3 clone expressed in L929 cells
Species:  Mouse
Tissue:  L929 cells
Response measured:  K+ current by patch clamp
References:  4,25,47,55
[3H] Dihydrocorreolide or [(3H)]-trans-NPCO-DSC binding assay in HEK293 cells expressing Kv1.3
Species:  Rat
Tissue:  HEK293 cells
Response measured:  Binding or Displacement
References:  28,54
Kv1.3 clone expression
Species:  Human
Tissue:  CHO or HEK293 cells
Response measured:  K+ current by patch clamp
References:  29,46
Kv1.3 clone expression
Species:  Rat
Tissue:  Xenopus laevis Oocytes
Response measured:  K+ current by patch clamp
References:  16,31,59
Physiological Functions
Homomeric Kv1.3 channels in the olfactory bulb neurons carry 60 - 80% of the Kv current in these cells which shows an involvement in signal transduction. Kv1.3 -/- mice have a "Super Smeller" phenotype with a lower threshold for smell detection.
Species:  Mouse
Tissue:  Olfactory neurons, olfactory cortex
References:  7,18
Kv1.3 is involved in rat oligodendrocyte progenitor proliferation and G1/S phase progression.
Species:  Rat
Tissue:  Oligodendrocyte progenitor cells
References:  1,12
Kv1.3 is involved in proliferation, oxidative burst and microglia mediated neuronal killing
Species:  Rat
Tissue:  Cultured rat microglia
References:  21,32,35
Kv1.3 is involved in T-lymphocyte volume regulation and possibly apoptosis.
Species:  Human
Tissue:  Jurkat T-lymphocytes
References:  57,60
Kv1.3 is involved in T-lymphocyte volume regulation and possibly apoptosis.
Species:  Mouse
Tissue:  T-lymphocytes (CTLL-2)
References:  15
Kv1.3 is a voltage gated potassium channel in human T-lymphocytes, and regulates membrane potential and calcium signalling. Kv1.3 blockade results in inhibition of T-cell proliferation and cytokine secretion. It is more important in CCR7-effector memory T-cells than in naive and central memory T-cells.
Species:  Human
Tissue:  T-lymphocytes
References:  6,9,11,14,23,43,65
Kv1.3 is involved in the translocation of the glucose transporter, GLUT4, to the plasma membrane in adipocytes (based on biophysical properties of current, probably heteromultimer of various Kv1 channels and not a homomultimer of Kv1.3). This suggests that it is important in insulin sensitivity.
Species:  Mouse
Tissue:  Mouse adipocytes
References:  7,38,67
In macrophages, Kv1.3 is probably found as a heteromultimer with Kv1.5.
Kv1.3 blockers suppress proliferation of mouse bone marrow derived macrophages.
Species:  Mouse
Tissue:  Macrophages
References:  63-64
Physiological Functions Comments
Studies have also been carried out in macaque monkeys [51] and swine [34].
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0002078 abnormal glucose homeostasis PMID: 14981264 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0004130 abnormal muscle cell glucose uptake PMID: 12588802 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0001262 decreased body weight PMID: 12588802 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0002727 decreased circulating insulin level PMID: 14981264 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0008965 increased basal metabolism PMID: 12588802 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0002891 increased insulin sensitivity PMID: 14981264 
Kcna3tm1Gvd Kcna3tm1Gvd/Kcna3tm1Gvd
involves: 129S1/Sv * C57BL/6
MGI:96660  MP:0005659 increased resistance to diet-induced obesity PMID: 12588802 
Kcna3tm1Lys Kcna3tm1Lys/Kcna3tm1Lys
involves: 129/Sv * C57BL/6
MGI:96660  MP:0002169 no abnormal phenotype detected PMID: 12878608 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Multiple-Sclerosis, Type -1 Diabetes, Rheumatoid Arthritis, Psoriasis
OMIM:  126200, 222100, 604302, 177900
Role: 
Drugs: 
Side effects:  Inhibition of effector memory T-cells could potentially lead to reactivation of viral infections such as CMV.
Therapeutic use:  ShK derivative and PAP-1 are in clinical development
Comments: 
References:  3,5-6,34,62,65
Mutations not determined
Gene Expression and Pathophysiology
Kv1.3 expression is increased in activated effector memory T-cells and class-switched CD27+ memory B-cells. Naive and memory T-cells and IgD+ B-cells in contrast, up-regulate KCa3.1 following activation.
Tissue or cell type:  T-Lymphocytes
Pathophysiology:  Up-regulation of Kv1.3 has no real pathophysiological effect, but allows to selectively target effector memory T-cells.
Species:  Human
Technique: 
References:  6,65-66
Gene Expression and Pathophysiology Comments
Kv1.3 -/- mouse has no immune phenotype [33].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  T1645C is associated with imparied glucose tolerance and lower insulin sensitivity.
Amino acids:  1
References:  61
Biologically Significant Variant Comments
A total of 5 SNPs have been identified; T548C, G697T, A845G, T1645C, G2069A.
General Comments
Kv1.3 can coassemble with other members of the Kv1 family, in heteromultimers. It cannot, however, co-assemble with members of other Kv families.

Like other members of the family, it has an intronless coding region.

REFERENCES

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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: Kv1.3. Last modified on 11/02/2014. Accessed on 24/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=540.

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