Nomenclature: Kv1.4

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. 

Contents

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 653 11p14.3-15.2 KCNA4 potassium voltage-gated channel, shaker-related subfamily, member 4 23,39
Mouse 6 1 654 2 E Kcna4 potassium voltage-gated channel, shaker-related subfamily, member 4 39
Rat 6 1 654 3q33 Kcna4 potassium voltage-gated channel, shaker-related subfamily, member 4 38
Previous and Unofficial Names
HuK (II)
hPCN2
HK1
RHK1
RK4
RK8
MK4
Kv1.4
RCK4
KCNA4L
potassium voltage-gated channel, shaker-related subfamily, member 4-like
KCHAN
Kv4
RK3
potassium voltage gated channel, shaker related subfamily, member 4
potassium voltage-gated channel subfamily A member 4
potassium voltage-gated channel, shaker-related subfamily, member 4
voltage-gated potassium channel subunit Kv1.4
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
KVβ 4,9,18-19,26-27
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
KChAP 15
α-actinin-2 5
SAP90 24
SAP97 14
σ-receptor 2
PSD-95 14,37
CamKII 30
Functional Characteristics
KA
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ > Na+
References:  25
Species:  Rat
Rank order:  K+ [5.0 pS]
References:  34
Species:  Human
Macroscopic current rectification:  Ik, A-Type current, fast-inactivating
References:  25
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -34.0 - 25 Xenopus laevis oocyte Human
Inactivation  -62.0 47.0 25
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -22.0 3.0 34 Xenopus laevis oocyte Rat
Inactivation  -74.0 - 34
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
CP-339818 Mm - 6.5 pIC50 - - 20
pIC50 6.5 [20]
nicardipine Rn - 6.1 pIC50 - - 8
pIC50 6.1 [8]
quinidine Rn - 3.7 pIC50 - - 40
pIC50 3.7 [40]
fampridine Rn - 1.9 pIC50 - - 34
pIC50 1.9 [34]
View species-specific channel blocker tables
Tissue Distribution
Insulinoma and islet.
Species:  Human
Technique:  Northern Blot
References:  22
Heart
Species:  Human
Technique:  Northern Blot
References:  36
Brain (olfactory bulb, corpus striatum > hippocampus, superior and inferior colliculus > cerebral cortex, midbrain basal ganglia > pons/medulla).
Species:  Rat
Technique:  Northern Blot, Immunohistochemistry and RT-PCR
References:  3,25,31-32
Heart
Species:  Rat
Technique:  Northern Blot
References:  29,38
Pancreatic islet.
Species:  Rat
Technique:  RT-PCR
References:  16,35
Skeletal muscle, arterial smooth muscle, retina.
Species:  Rat
Technique:  Northern Blot and Immunocytochemistry
References:  11,17,33
Functional Assays
Two electrode voltage clamp
Species:  Human
Tissue:  Xenopus laevis oocytes
Response measured:  Rapidly inactivated
References:  25
Molecular clone and voltage clamp
Species:  Rat
Tissue:  Xenopus laevis oocytes
Response measured:  A-type current
References:  31,34
Physiological Functions
After hypolarisation or early repolarisation.
Species:  Rat
Tissue:  Brain, heart.
References:  7,28,34
Potential mediators of repolarisation.
Species:  Rat
Tissue:  Pancreatic islet.
References:  16,35
Potential mediators of repolarisation.
Species:  Human
Tissue:  Heart, pancreatic islet.
References:  22,28
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna4tm1Lndn Kcna4tm1Lndn/Kcna4tm1Lndn
involves: 129S4/SvJae * C57BL/6
MGI:96661  MP:0002064 seizures PMID: 9547391 
Gene Expression and Pathophysiology
KV1.4 expression decreased after myocardial infarction.
Tissue or cell type:  Rat heart.
Pathophysiology:  Decrease after MI.
Species:  Rat
Technique:  In vivo
References:  6,10,13
KV1.4 mRNA expression increases in AΒ25-35-treated rat hippocampus.
Tissue or cell type:  Rat brain.
Pathophysiology:  Spatial memory deficit.
Species:  Rat
Technique:  In vivo
References:  21
General Comments
Kv1.4 can coassemble with other Kv1 family members in heteromultimers but not with members of the other Kv families.

Intronless coding region.

Mouse Kv1.4 mRNA contains an internal ribosome entry site in its 5-noncoding region and may be translated by cap-independent mechanisms [1,12].

REFERENCES

1. Albrecht B, Weber K, Pongs O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept. Channels3 (3): 213-20. [PMID:8821794]

2. Aydar E, Palmer CP, Klyachko VA, Jackson MB. (2002) The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron34 (3): 399-410. [PMID:11988171]

3. Beckh S, Pongs O. (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J.9 (3): 777-82. [PMID:2311579]

4. Bekele-Arcuri Z, Matos MF, Manganas L, Strassle BW, Monaghan MM, Rhodes KJ, Trimmer JS. (1996) Generation and characterization of subtype-specific monoclonal antibodies to K+ channel alpha- and beta-subunit polypeptides. Neuropharmacology35 (7): 851-65. [PMID:8938716]

5. Cukovic D, Lu GW, Wible B, Steele DF, Fedida D. (2001) A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of alpha-actinin-2. FEBS Lett.498 (1): 87-92. [PMID:11389904]

6. Gidh-Jain M, Huang B, Jain P, el-Sherif N. (1996) Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction. Circ. Res.79 (4): 669-75. [PMID:8831490]

7. Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol. Rev.57 (4): 473-508. [PMID:16382104]

8. Hatano N, Ohya S, Muraki K, Giles W, Imaizumi Y. (2003) Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells. Br. J. Pharmacol.139 (3): 533-44. [PMID:12788813]

9. Heinemann SH, Rettig J, Graack HR, Pongs O. (1996) Functional characterization of Kv channel beta-subunits from rat brain. J. Physiol. (Lond.)493 ( Pt 3): 625-33. [PMID:8799886]

10. Huang B, Qin D, El-Sherif N. (2001) Spatial alterations of Kv channels expression and K(+) currents in post-MI remodeled rat heart. Cardiovasc. Res.52 (2): 246-54. [PMID:11684072]

11. Höltje M, Brunk I, Grosse J, Beyer E, Veh RW, Bergmann M, Grosse G, Ahnert-Hilger G. (2007) Differential distribution of voltage-gated potassium channels Kv 1.1-Kv1.6 in the rat retina during development. J. Neurosci. Res.85 (1): 19-33. [PMID:17075900]

12. Jang GM, Leong LE, Hoang LT, Wang PH, Gutman GA, Semler BL. (2004) Structurally distinct elements mediate internal ribosome entry within the 5'-noncoding region of a voltage-gated potassium channel mRNA. J. Biol. Chem.279 (46): 47419-30. [PMID:15339906]

13. Kaprielian R, Wickenden AD, Kassiri Z, Parker TG, Liu PP, Backx PH. (1999) Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction. J. Physiol. (Lond.)517 ( Pt 1): 229-45. [PMID:10226162]

14. Kim E, Sheng M. (1996) Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology35 (7): 993-1000. [PMID:8938729]

15. Kuryshev YA, Wible BA, Gudz TI, Ramirez AN, Brown AM. (2001) KChAP/Kvbeta1.2 interactions and their effects on cardiac Kv channel expression. Am. J. Physiol., Cell Physiol.281 (1): C290-9. [PMID:11401852]

16. MacDonald PE, Ha XF, Wang J, Smukler SR, Sun AM, Gaisano HY, Salapatek AM, Backx PH, Wheeler MB. (2001) Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol. Endocrinol.15 (8): 1423-35. [PMID:11463864]

17. Matsubara H, Liman ER, Hess P, Koren G. (1991) Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles. J. Biol. Chem.266 (20): 13324-8. [PMID:1712780]

18. McCormack K, McCormack T, Tanouye M, Rudy B, Stühmer W. (1995) Alternative splicing of the human Shaker K+ channel beta 1 gene and functional expression of the beta 2 gene product. FEBS Lett.370 (1-2): 32-6. [PMID:7649300]

19. Morales MJ, Castellino RC, Crews AL, Rasmusson RL, Strauss HC. (1995) A novel beta subunit increases rate of inactivation of specific voltage-gated potassium channel alpha subunits. J. Biol. Chem.270 (11): 6272-7. [PMID:7890764]

20. Nguyen A, Kath JC, Hanson DC, Biggers MS, Canniff PC, Donovan CB, Mather RJ, Bruns MJ, Rauer H, Aiyar J, Lepple-Wienhues A, Gutman GA, Grissmer S, Cahalan MD, Chandy KG. (1996) Novel nonpeptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol. Pharmacol.50 (6): 1672-9. [PMID:8967992]

21. Pan Y, Xu X, Tong X, Wang X. (2004) Messenger RNA and protein expression analysis of voltage-gated potassium channels in the brain of Abeta(25-35)-treated rats. J. Neurosci. Res.77 (1): 94-9. [PMID:15197742]

22. Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, Steiner DF. (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc. Natl. Acad. Sci. U.S.A.88 (1): 53-7. [PMID:1986382]

23. Philipson LH, Schaefer K, LaMendola J, Bell GI, Steiner DF. (1990) Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4. Nucleic Acids Res.18 (23): 7160. [PMID:2263489]

24. Piserchio A, Pellegrini M, Mehta S, Blackman SM, Garcia EP, Marshall J, Mierke DF. (2002) The PDZ1 domain of SAP90. Characterization of structure and binding. J. Biol. Chem.277 (9): 6967-73. [PMID:11744724]

25. Po S, Snyders DJ, Baker R, Tamkun MM, Bennett PB. (1992) Functional expression of an inactivating potassium channel cloned from human heart. Circ. Res.71 (3): 732-6. [PMID:1499114]

26. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, Trimmer JS. (1995) Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain. J. Neurosci.15 (7 Pt 2): 5360-71. [PMID:7623158]

27. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, Trimmer JS. (1997) Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits with Kv1 alpha-subunits in mammalian brain K+ channel complexes. J. Neurosci.17 (21): 8246-58. [PMID:9334400]

28. Roberds SL, Knoth KM, Po S, Blair TA, Bennett PB, Hartshorne RP, Snyders DJ, Tamkun MM. (1993) Molecular biology of the voltage-gated potassium channels of the cardiovascular system. J. Cardiovasc. Electrophysiol.4 (1): 68-80. [PMID:8287238]

29. Roberds SL, Tamkun MM. (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc. Natl. Acad. Sci. U.S.A.88 (5): 1798-802. [PMID:1705709]

30. Roeper J, Lorra C, Pongs O. (1997) Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase. J. Neurosci.17 (10): 3379-91. [PMID:9133364]

31. Sheng M, Liao YJ, Jan YN, Jan LY. (1993) Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature365 (6441): 72-5. [PMID:8361540]

32. Sheng M, Tsaur ML, Jan YN, Jan LY. (1992) Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron9 (2): 271-84. [PMID:1497894]

33. Standen NB, Quayle JM. (1998) K+ channel modulation in arterial smooth muscle. Acta Physiol. Scand.164 (4): 549-57. [PMID:9887977]

34. Stühmer W, Ruppersberg JP, Schröter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O. (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J.8 (11): 3235-44. [PMID:2555158]

35. Su J, Yu H, Lenka N, Hescheler J, Ullrich S. (2001) The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1. Pflugers Arch.442 (1): 49-56. [PMID:11374068]

36. Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, Glover DM. (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J.5 (3): 331-7. [PMID:2001794]

37. Topinka JR, Bredt DS. (1998) N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron20 (1): 125-34. [PMID:9459448]

38. Tseng-Crank JC, Tseng GN, Schwartz A, Tanouye MA. (1990) Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library. FEBS Lett.268 (1): 63-8. [PMID:2384173]

39. Wymore RS, Korenberg JR, Kinoshita KD, Aiyar J, Coyne C, Chen XN, Hustad CM, Copeland NG, Gutman GA, Jenkins NA. (1994) Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human 11p14.3-p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics20 (2): 191-202. [PMID:8020965]

40. Yamagishi T, Ishii K, Taira N. (1995) Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4. Eur. J. Pharmacol.281 (2): 151-9. [PMID:7589202]

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: Kv1.4. Last modified on 11/10/2012. Accessed on 25/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=541.

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