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Kv1.4

Family: Voltage-gated potassium channels

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Associated Proteins
Ion Selectivity and Conductance
Voltage Dependence
Pore Blockers
Tissue Distribution
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Gene Expression and Pathophysiology
General Comments
References
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 100630 (Hs), 100470 (Mm), 101243 (Rn)
Ensembl ENSG00000182255 (Hs), ENSMUSG00000042604 (Mm), ENSRNOG00000004918 (Rn)
Entrez Gene 3739 (Hs), 16492 (Mm), 25469 (Rn)
GeneCards KCNA4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Kcna4 (Mm)
HomoloGene 20514 (Hs)
Human Protein Reference Database 01444 (Hs)
InterPro P22459 (Hs), Q61423 (Mm), P15385 (Rn)
KEGG Gene hsa:3739 (Hs), mmu:16492 (Mm), rno:25469 (Rn)
OMIM 176266 (Hs)
PharmGKB Gene PA207 (Hs)
PhosphoSitePlus P22459 (Hs), Q61423 (Mm), P15385 (Rn)
Protein Ontology (PRO) PRO:000000683 (Hs)
RefSeq Nucleotide NM_002233 (Hs), NM_021275 (Mm), NM_012971 (Rn)
RefSeq Protein NP_002224 (Hs), NP_067250 (Mm), NP_037103 (Rn)
TreeFam ENSG00000182255 (Hs), ENSMUSG00000042604 (Mm), ENSRNOG00000004918 (Rn)
UniGene Hs. 592002 (Hs)
UniProt P22459 (Hs), Q61423 (Mm), P15385 (Rn)
Wikipedia Kv1.4
Potassium channels
Search for 3D structures on the PDB
Search by keyword: Voltage-gated potassium channels Kv1.4 Search by accession number: P15385, Q61423, P22459
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
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
Pore Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Affinity Units Concentration range (M) Holding voltage (mV) Reference
CP-339818 Mm 6.5 pIC50 - - 20
nicardipine Rn 6.1 pIC50 - - 8
quinidine Rn 3.7 pIC50 - - 40
4-aminopyridine Rn 1.9 pIC50 - - 34
View species-specific pore 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

Click here to show/hide data

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

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1. Albrecht, B; Weber, K; Pongs, O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept. Channels, 3 (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. Neuron, 34 (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. Neuropharmacology, 35 (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. Neuropharmacology, 35 (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. Nature, 365 (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. Neuron, 9 (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. Neuron, 20 (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. Genomics, 20 (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 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=541.


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