Potassium voltage-gated channel subfamily A member 1


Potassium voltage-gated channel subfamily A member 1
  • Voltage-gated K(+) channel HuKI
  • Voltage-gated potassium channel HBK1
  • Voltage-gated potassium channel subunit Kv1.1
Gene Name
Amino acid sequence
>lcl|BSEQ0019011|Potassium voltage-gated channel subfamily A member 1
Number of residues
Molecular Weight
Theoretical pI
GO Classification
delayed rectifier potassium channel activity / potassium channel activity / potassium ion transmembrane transporter activity / voltage-gated potassium channel activity
cell communication by electrical coupling / cellular protein localization / cellular response to magnesium ion / detection of mechanical stimulus involved in sensory perception of pain / detection of mechanical stimulus involved in sensory perception of touch / hippocampus development / magnesium ion homeostasis / neuroblast proliferation / neuromuscular process / neuronal action potential / neuronal signal transduction / potassium ion transmembrane transport / potassium ion transport / protein homooligomerization / regulation of membrane potential / regulation of muscle contraction / startle response / synaptic transmission
apical plasma membrane / axon terminus / cell junction / cell surface / cytoplasmic membrane-bounded vesicle / cytosol / dendrite / endoplasmic reticulum / integral component of plasma membrane / juxtaparanode region of axon / neuronal cell body / paranode region of axon / perikaryon / plasma membrane / presynaptic membrane / synapse / voltage-gated potassium channel complex
General Function
Voltage-gated potassium channel activity
Specific Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:23903368, PubMed:19307729).
Pfam Domain Function
Transmembrane Regions
165-186 221-242 254-274 288-308 324-345 387-415
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019012|Potassium voltage-gated channel subfamily A member 1 (KCNA1)
Chromosome Location
External Identifiers
UniProtKB IDQ09470
UniProtKB Entry NameKCNA1_HUMAN
GenBank Protein ID186663
GenBank Gene IDL02750
GenAtlas IDKCNA1
General References
  1. Ramaswami M, Gautam M, Kamb A, Rudy B, Tanouye MA, Mathew MK: Human potassium channel genes: Molecular cloning and functional expression. Mol Cell Neurosci. 1990 Dec;1(3):214-23. [PubMed:19912772]
  2. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [PubMed:16541075]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  4. Freeman SN, Conley EC, Brennand JC, Russell NJ, Brammar WJ: Cloning and characterization of a cDNA encoding a human brain potassium channel. Biochem Soc Trans. 1990 Oct;18(5):891-2. [PubMed:2128063]
  5. Rasband MN, Trimmer JS: Subunit composition and novel localization of K+ channels in spinal cord. J Comp Neurol. 2001 Jan 1;429(1):166-76. [PubMed:11086297]
  6. Hoopengardner B, Bhalla T, Staber C, Reenan R: Nervous system targets of RNA editing identified by comparative genomics. Science. 2003 Aug 8;301(5634):832-6. [PubMed:12907802]
  7. Gubitosi-Klug RA, Mancuso DJ, Gross RW: The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5964-8. Epub 2005 Apr 18. [PubMed:15837928]
  8. Baranauskas G: Ionic channel function in action potential generation: current perspective. Mol Neurobiol. 2007 Apr;35(2):129-50. [PubMed:17917103]
  9. Usman H, Mathew MK: Potassium channel regulator KCNRG regulates surface expression of Shaker-type potassium channels. Biochem Biophys Res Commun. 2010 Jan 15;391(3):1301-5. doi: 10.1016/j.bbrc.2009.11.143. Epub 2009 Dec 5. [PubMed:19968958]
  10. Tomlinson SE, Tan SV, Kullmann DM, Griggs RC, Burke D, Hanna MG, Bostock H: Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1. Brain. 2010 Dec;133(Pt 12):3530-40. doi: 10.1093/brain/awq318. Epub 2010 Nov 23. [PubMed:21106501]
  11. Ma Z, Lavebratt C, Almgren M, Portwood N, Forsberg LE, Branstrom R, Berglund E, Falkmer S, Sundler F, Wierup N, Bjorklund A: Evidence for presence and functional effects of Kv1.1 channels in beta-cells: general survey and results from mceph/mceph mice. PLoS One. 2011 Apr 5;6(4):e18213. doi: 10.1371/journal.pone.0018213. [PubMed:21483673]
  12. Lallet-Daher H, Wiel C, Gitenay D, Navaratnam N, Augert A, Le Calve B, Verbeke S, Carling D, Aubert S, Vindrieux D, Bernard D: Potassium channel KCNA1 modulates oncogene-induced senescence and transformation. Cancer Res. 2013 Aug 15;73(16):5253-65. doi: 10.1158/0008-5472.CAN-12-3690. Epub 2013 Jun 17. [PubMed:23774215]
  13. San-Cristobal P, Lainez S, Dimke H, de Graaf MJ, Hoenderop JG, Bindels RJ: Ankyrin-3 is a novel binding partner of the voltage-gated potassium channel Kv1.1 implicated in renal magnesium handling. Kidney Int. 2014 Jan;85(1):94-102. doi: 10.1038/ki.2013.280. Epub 2013 Jul 31. [PubMed:23903368]
  14. Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, Litt M: Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. 1994 Oct;8(2):136-40. [PubMed:7842011]
  15. Browne DL, Brunt ER, Griggs RC, Nutt JG, Gancher ST, Smith EA, Litt M: Identification of two new KCNA1 mutations in episodic ataxia/myokymia families. Hum Mol Genet. 1995 Sep;4(9):1671-2. [PubMed:8541859]
  16. Adelman JP, Bond CT, Pessia M, Maylie J: Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron. 1995 Dec;15(6):1449-54. [PubMed:8845167]
  17. Comu S, Giuliani M, Narayanan V: Episodic ataxia and myokymia syndrome: a new mutation of potassium channel gene Kv1.1. Ann Neurol. 1996 Oct;40(4):684-7. [PubMed:8871592]
  18. Scheffer H, Brunt ER, Mol GJ, van der Vlies P, Stulp RP, Verlind E, Mantel G, Averyanov YN, Hofstra RM, Buys CH: Three novel KCNA1 mutations in episodic ataxia type I families. Hum Genet. 1998 Apr;102(4):464-6. [PubMed:9600245]
  19. Zuberi SM, Eunson LH, Spauschus A, De Silva R, Tolmie J, Wood NW, McWilliam RC, Stephenson JB, Kullmann DM, Hanna MG: A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy. Brain. 1999 May;122 ( Pt 5):817-25. [PubMed:10355668]
  20. Eunson LH, Rea R, Zuberi SM, Youroukos S, Panayiotopoulos CP, Liguori R, Avoni P, McWilliam RC, Stephenson JB, Hanna MG, Kullmann DM, Spauschus A: Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol. 2000 Oct;48(4):647-56. [PubMed:11026449]
  21. Knight MA, Storey E, McKinlay Gardner RJ, Hand P, Forrest SM: Identification of a novel missense mutation L329I in the episodic ataxia type 1 gene KCNA1--a challenging problem. Hum Mutat. 2000 Oct;16(4):374. [PubMed:11013453]
  22. Maylie B, Bissonnette E, Virk M, Adelman JP, Maylie JG: Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-type inactivation. J Neurosci. 2002 Jun 15;22(12):4786-93. [PubMed:12077175]
  23. Lee H, Wang H, Jen JC, Sabatti C, Baloh RW, Nelson SF: A novel mutation in KCNA1 causes episodic ataxia without myokymia. Hum Mutat. 2004 Dec;24(6):536. [PubMed:15532032]
  24. Imbrici P, D'Adamo MC, Kullmann DM, Pessia M: Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 and Kv1.4-1.1/Kvbeta1.2. Eur J Neurosci. 2006 Dec;24(11):3073-83. [PubMed:17156368]
  25. Chen H, von Hehn C, Kaczmarek LK, Ment LR, Pober BR, Hisama FM: Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia. Neurogenetics. 2007 Apr;8(2):131-5. Epub 2006 Nov 29. [PubMed:17136396]
  26. Glaudemans B, van der Wijst J, Scola RH, Lorenzoni PJ, Heister A, van der Kemp AW, Knoers NV, Hoenderop JG, Bindels RJ: A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia. J Clin Invest. 2009 Apr;119(4):936-42. doi: 10.1172/JCI36948. Epub 2009 Mar 23. [PubMed:19307729]
  27. van der Wijst J, Glaudemans B, Venselaar H, Nair AV, Forst AL, Hoenderop JG, Bindels RJ: Functional analysis of the Kv1.1 N255D mutation associated with autosomal dominant hypomagnesemia. J Biol Chem. 2010 Jan 1;285(1):171-8. doi: 10.1074/jbc.M109.041517. Epub 2009 Nov 10. [PubMed:19903818]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00753Isofluraneapproved, vet_approvedyesinducerDetails
DB01028Methoxyfluraneapproved, investigational, vet_approvedyesinducerDetails
DB08837Tetraethylammoniumexperimental, investigationalunknownblockerDetails
DB11640Amifampridineapproved, investigationalyesblockerDetails
DB00228Enfluraneapproved, investigational, vet_approvedunknowninhibitoractivatorDetails
DB01069Promethazineapproved, investigationalunknowninducerDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknowninhibitorDetails