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词条 KCNA3
释义

  1. Function

  2. Clinical significance

      Autoimmune    Metabolic    Neurodegeneration  

  3. Blockers

  4. See also

  5. References

  6. External links

{{Infobox_gene}}Potassium voltage-gated channel, shaker-related subfamily, member 3, also known as KCNA3 or Kv1.3, is a protein that in humans is encoded by the KCNA3 gene.[1][2][3]

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes – shaker, shaw, shab, and shal – have been identified in Drosophila, and each has been shown to have human homolog(s).

This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. It plays an essential role in T cell proliferation and activation. This gene appears to be intronless and is clustered together with KCNA2 and KCNA10 genes on chromosome 1.[1]

Function

KCNA3 encodes the voltage-gated Kv1.3 channel, which is expressed in T and B lymphocytes.[2][4][5][6][7][8][9] All human T cells express roughly 300 Kv1.3 channels per cell along with 10-20 calcium-activated KCa3.1 channels.[10][11] Upon activation, naive and central memory T cells increase expression of the KCa3.1 channel to approximately 500 channels per cell, while effector-memory T cells increase expression of the Kv1.3 channel.[10][11] Among human B cells, naive and early memory B cells express small numbers of Kv1.3 and KCa3.1 channels when they are quiescent, and augment KCa3.1 expression after activation.[12] In contrast, class-switched memory B cells express high numbers of Kv1.3 channels per cell (about 1500/cell) and this number increases after activation.[12]

Kv1.3 is physically coupled through a series of adaptor proteins to the T-cell receptor signaling complex and it traffics to the immunological synapse during antigen presentation.[13][14] However, blockade of the channel does not prevent immune synapse formation.[14] Kv1.3 and KCa3.1 regulate membrane potential and calcium signaling of T cells.[10] Calcium entry through the CRAC channel is promoted by potassium efflux through the Kv1.3 and KCa3.1 potassium channels.[14][23]

Blockade of Kv1.3 channels in effector-memory T cells suppresses calcium signaling, cytokine production (interferon-gamma, interleukin 2) and cell proliferation.[10][11][14] In vivo, Kv1.3 blockers paralyze effector-memory T cells at the sites of inflammation and prevent their reactivation in inflamed tissues.[15] In contrast, Kv1.3 blockers do not affect the homing to and motility within lymph nodes of naive and central memory T cells, most likely because these cells express the KCa3.1 channel and are, therefore, protected from the effect of Kv1.3 blockade.[15]

Kv1.3 has been reported to be expressed in the inner mitochondrial membrane in lymphocytes.[16] The apoptotic protein Bax has been suggested to insert into the outer mitochondrial membrane and occlude the pore of Kv1.3 via a lysine residue.[17] Thus, Kv1.3 modulation may be one of many mechanisms that contribute to apoptosis.[16][17][18][19][20]

Clinical significance

Autoimmune

In patients with multiple sclerosis (MS), disease-associated myelin-specific T cells from the blood are predominantly co-stimulation-independent[21] effector-memory T cells that express high numbers of Kv1.3 channels.[11][14] T cells in MS lesions in postmortem brain lesions are also predominantly effector-memory T cells that express high levels of the Kv1.3 channel.[22] In children with type-1 diabetes mellitus, the disease-associated insulin- and GAD65-specific T cells isolated from the blood are effector-memory T cells that express high numbers of Kv1.3 channels, and the same is true of T cells from the synovial joint fluid of patients with rheumatoid arthritis.[14] T cells with other antigen specificities in these patients were naive or central memory T cells that upregulate the KCa3.1 channel upon activation.[14] Consequently, it should be possible to selectively suppress effector-memory T cells with a Kv1.3-specific blocker and thereby ameliorate many autoimmune diseases without compromising the protective immune response. In proof-of-concept studies, Kv1.3 blockers have prevented and treated disease in rat models of multiple sclerosis, type-1 diabetes mellitus, rheumatoid arthritis, contact dermatitis, and delayed-type hypersensitivity.[14][23][24][25][26]

At therapeutic concentrations, the blockers did not cause any clinically evident toxicity in rodents,[14][23] and it did not compromise the protective immune response to acute influenza viral infection and acute chlamydia bacterial infection.[15] Many groups are developing Kv1.3 blockers for the treatment of autoimmune diseases.[27]

Metabolic

Kv1.3 is also considered a therapeutic target for the treatment of obesity,[28][29] for enhancing peripheral insulin sensitivity in patients with type-2 diabetes mellitus,[30] and for preventing bone resorption in periodontal disease.[31] A genetic variation in the Kv1.3 promoter region is associated with low insulin sensitivity and impaired glucose tolerance.[32]

Neurodegeneration

Kv1.3 channels have been found to be highly expressed by activated and plaque-associated microglia in human Alzheimer’s disease (AD) post-mortem brains [33] as well as in mouse models of AD pathology.[34] Patch-clamp recordings and flow cytometric studies performed on acutely isolated mouse microglia have confirmed upregulation of Kv1.3 channels with disease progression in mouse AD models.[34][35] The Kv1.3 channel gene has also been found to be a regulator of pro-inflammatory microglial responses.[36] Selective blockade of Kv1.3 channels by the small molecule Pap1 as well as a peptide sea anemone toxin-based peptide ShK-223 have been found to limit amyloid beta plaque burden in mouse AD models, potentially via augmented clearance by microglia.[34][35]

Blockers

Kv1.3 is blocked[31] by several peptides from venomous creatures including scorpions (ADWX1, OSK1,[37] margatoxin,[38] kaliotoxin, charybdotoxin, noxiustoxin, anuroctoxin)[39][40] and sea anemone (ShK,[41][42][43][44][45] ShK-F6CA, ShK-186, ShK-192,[46] BgK[47]), and by small molecule compounds (e.g., PAP-1,[48] Psora-4,[49] correolide,[50] benzamides,[51] CP339818,[52] progesterone[53] and the anti-lepromatous drug clofazimine[54]). The Kv1.3 blocker clofazimine has been reported to be effective in the treatment of chronic graft-versus-host disease,[55] cutaneous lupus,[56][57] and pustular psoriasis[58][59] in humans. Furthermore, clofazimine in combination with the antibiotics clarithromycin and rifabutin induced remission for about 2 years in patients with Crohn's disease, but the effect was temporary; the effect was thought to be due to anti-mycobacterial activity, but could well have been an immunomodulatory effect by clofazimine.[60]

See also

  • Voltage-gated potassium channel

References

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2. ^1 {{cite journal | vauthors = Grissmer S, Dethlefs B, Wasmuth JJ, Goldin AL, Gutman GA, Cahalan MD, Chandy KG | title = Expression and chromosomal localization of a lymphocyte K + channel gene | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 23 | pages = 9411–5 | date = December 1990 | pmid = 2251283 | pmc = 55175 | doi = 10.1073/pnas.87.23.9411 }}
3. ^{{cite journal | vauthors = Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X | title = International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 473–508 | date = December 2005 | pmid = 16382104 | doi = 10.1124/pr.57.4.10 }}
4. ^{{cite journal | vauthors = DeCoursey TE, Chandy KG, Gupta S, Cahalan MD | title = Voltage-gated K + channels in human T lymphocytes: a role in mitogenesis? | journal = Nature | volume = 307 | issue = 5950 | pages = 465–8 | year = 1984 | pmid = 6320007 | doi = 10.1038/307465a0 }}
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6. ^{{cite journal | vauthors = Chandy KG, DeCoursey TE, Cahalan MD, McLaughlin C, Gupta S | title = Voltage-gated potassium channels are required for human T lymphocyte activation | journal = The Journal of Experimental Medicine | volume = 160 | issue = 2 | pages = 369–85 | date = August 1984 | pmid = 6088661 | pmc = 2187449 | doi = 10.1084/jem.160.2.369 }}
7. ^{{cite journal | vauthors = Chandy KG, Williams CB, Spencer RH, Aguilar BA, Ghanshani S, Tempel BL, Gutman GA | title = A family of three mouse potassium channel genes with intronless coding regions | journal = Science | volume = 247 | issue = 4945 | pages = 973–5 | date = February 1990 | pmid = 2305265 | doi = 10.1126/science.2305265 }}
8. ^{{cite journal | vauthors = Douglass J, Osborne PB, Cai YC, Wilkinson M, Christie MJ, Adelman JP | title = Characterization and functional expression of a rat genomic DNA clone encoding a lymphocyte potassium channel | journal = Journal of Immunology | volume = 144 | issue = 12 | pages = 4841–50 | date = June 1990 | pmid = 2351830 | doi = | url = http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=2351830 }}
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10. ^1 2 3 {{cite journal | vauthors = Chandy KG, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD | title = K + channels as targets for specific immunomodulation | journal = Trends in Pharmacological Sciences | volume = 25 | issue = 5 | pages = 280–9 | date = May 2004 | pmid = 15120495 | pmc = 2749963 | doi = 10.1016/j.tips.2004.03.010 }}
11. ^1 2 3 {{cite journal | vauthors = Wulff H, Calabresi PA, Allie R, Yun S, Pennington M, Beeton C, Chandy KG | title = The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS | journal = The Journal of Clinical Investigation | volume = 111 | issue = 11 | pages = 1703–13 | date = June 2003 | pmid = 12782673 | pmc = 156104 | doi = 10.1172/JCI16921 }}
12. ^1 {{cite journal | vauthors = Wulff H, Knaus HG, Pennington M, Chandy KG | title = K + channel expression during B cell differentiation: implications for immunomodulation and autoimmunity | journal = Journal of Immunology | volume = 173 | issue = 2 | pages = 776–86 | date = July 2004 | pmid = 15240664 | doi = 10.4049/jimmunol.173.2.776 }}
13. ^{{cite journal | vauthors = Panyi G, Vámosi G, Bacsó Z, Bagdány M, Bodnár A, Varga Z, Gáspár R, Mátyus L, Damjanovich S | title = Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 5 | pages = 1285–90 | date = February 2004 | pmid = 14745040 | pmc = 337045 | doi = 10.1073/pnas.0307421100 }}
14. ^1 2 3 4 5 6 7 8 {{cite journal | vauthors = Beeton C, Wulff H, Standifer NE, Azam P, Mullen KM, Pennington MW, Kolski-Andreaco A, Wei E, Grino A, Counts DR, Wang PH, LeeHealey CJ, S Andrews B, Sankaranarayanan A, Homerick D, Roeck WW, Tehranzadeh J, Stanhope KL, Zimin P, Havel PJ, Griffey S, Knaus HG, Nepom GT, Gutman GA, Calabresi PA, Chandy KG | title = Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 46 | pages = 17414–9 | date = November 2006 | pmid = 17088564 | pmc = 1859943 | doi = 10.1073/pnas.0605136103 }}
15. ^1 2 3 {{cite journal | vauthors = Matheu MP, Beeton C, Garcia A, Chi V, Rangaraju S, Safrina O, Monaghan K, Uemura MI, Li D, Pal S, de la Maza LM, Monuki E, Flügel A, Pennington MW, Parker I, Chandy KG, Cahalan MD | title = Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block | journal = Immunity | volume = 29 | issue = 4 | pages = 602–14 | date = October 2008 | pmid = 18835197 | pmc = 2732399 | doi = 10.1016/j.immuni.2008.07.015 }}
16. ^1 {{cite journal | vauthors = Szabò I, Bock J, Jekle A, Soddemann M, Adams C, Lang F, Zoratti M, Gulbins E | title = A novel potassium channel in lymphocyte mitochondria | journal = The Journal of Biological Chemistry | volume = 280 | issue = 13 | pages = 12790–8 | date = April 2005 | pmid = 15632141 | doi = 10.1074/jbc.M413548200 }}
17. ^1 {{cite journal | vauthors = Szabó I, Bock J, Grassmé H, Soddemann M, Wilker B, Lang F, Zoratti M, Gulbins E | title = Mitochondrial potassium channel Kv1.3 mediates Bax-induced apoptosis in lymphocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 39 | pages = 14861–6 | date = September 2008 | pmid = 18818304 | pmc = 2567458 | doi = 10.1073/pnas.0804236105 }}
18. ^{{cite journal | vauthors = Szabò I, Gulbins E, Apfel H, Zhang X, Barth P, Busch AE, Schlottmann K, Pongs O, Lang F | title = Tyrosine phosphorylation-dependent suppression of a voltage-gated K + channel in T lymphocytes upon Fas stimulation | journal = The Journal of Biological Chemistry | volume = 271 | issue = 34 | pages = 20465–9 | date = August 1996 | pmid = 8702786 | doi = 10.1074/jbc.271.34.20465 }}
19. ^{{cite journal | vauthors = Storey NM, Gómez-Angelats M, Bortner CD, Armstrong DL, Cidlowski JA | title = Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 35 | pages = 33319–26 | date = August 2003 | pmid = 12807917 | doi = 10.1074/jbc.M300443200 }}
20. ^{{cite journal | vauthors = Franco R, DeHaven WI, Sifre MI, Bortner CD, Cidlowski JA | title = Glutathione depletion and disruption of intracellular ionic homeostasis regulate lymphoid cell apoptosis | journal = The Journal of Biological Chemistry | volume = 283 | issue = 52 | pages = 36071–87 | date = December 2008 | pmid = 18940791 | pmc = 2605975 | doi = 10.1074/jbc.M807061200 }}
21. ^{{cite journal | vauthors = Markovic-Plese S, Cortese I, Wandinger KP, McFarland HF, Martin R | title = CD4+CD28- costimulation-independent T cells in multiple sclerosis | journal = The Journal of Clinical Investigation | volume = 108 | issue = 8 | pages = 1185–94 | date = October 2001 | pmid = 11602626 | pmc = 209525 | doi = 10.1172/JCI12516 }}
22. ^{{cite journal | vauthors = Rus H, Pardo CA, Hu L, Darrah E, Cudrici C, Niculescu T, Niculescu F, Mullen KM, Allie R, Guo L, Wulff H, Beeton C, Judge SI, Kerr DA, Knaus HG, Chandy KG, Calabresi PA | title = The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 31 | pages = 11094–9 | date = August 2005 | pmid = 16043714 | pmc = 1182417 | doi = 10.1073/pnas.0501770102 }}
23. ^1 {{cite journal | vauthors = Beeton C, Wulff H, Barbaria J, Clot-Faybesse O, Pennington M, Bernard D, Cahalan MD, Chandy KG, Béraud E | title = Selective blockade of T lymphocyte K(+) channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 24 | pages = 13942–7 | date = November 2001 | pmid = 11717451 | pmc = 61146 | doi = 10.1073/pnas.241497298 }}
24. ^{{cite journal | vauthors = Beeton C, Pennington MW, Wulff H, Singh S, Nugent D, Crossley G, Khaytin I, Calabresi PA, Chen CY, Gutman GA, Chandy KG | title = Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases | journal = Molecular Pharmacology | volume = 67 | issue = 4 | pages = 1369–81 | date = April 2005 | pmid = 15665253 | pmc = 4275123 | doi = 10.1124/mol.104.008193 }}
25. ^{{cite journal | vauthors = Beeton C, Smith BJ, Sabo JK, Crossley G, Nugent D, Khaytin I, Chi V, Chandy KG, Pennington MW, Norton RS | title = The D-diastereomer of ShK toxin selectively blocks voltage-gated K + channels and inhibits T lymphocyte proliferation | journal = The Journal of Biological Chemistry | volume = 283 | issue = 2 | pages = 988–97 | date = January 2008 | pmid = 17984097 | doi = 10.1074/jbc.M706008200 }}
26. ^{{cite journal | vauthors = Azam P, Sankaranarayanan A, Homerick D, Griffey S, Wulff H | title = Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis | journal = The Journal of Investigative Dermatology | volume = 127 | issue = 6 | pages = 1419–29 | date = June 2007 | pmid = 17273162 | pmc = 1929164 | doi = 10.1038/sj.jid.5700717 }}
27. ^{{cite journal | vauthors = Wulff H, Beeton C, Chandy KG | title = Potassium channels as therapeutic targets for autoimmune disorders | journal = Current Opinion in Drug Discovery & Development | volume = 6 | issue = 5 | pages = 640–7 | date = September 2003 | pmid = 14579513 | doi = }}
28. ^{{cite journal | vauthors = Tucker K, Overton JM, Fadool DA | title = Kv1.3 gene-targeted deletion alters longevity and reduces adiposity by increasing locomotion and metabolism in melanocortin-4 receptor-null mice | journal = International Journal of Obesity | volume = 32 | issue = 8 | pages = 1222–32 | date = August 2008 | pmid = 18542083 | pmc = 2737548 | doi = 10.1038/ijo.2008.77 }}
29. ^{{cite journal | vauthors = Xu J, Koni PA, Wang P, Li G, Kaczmarek L, Wu Y, Li Y, Flavell RA, Desir GV | title = The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight | journal = Human Molecular Genetics | volume = 12 | issue = 5 | pages = 551–9 | date = March 2003 | pmid = 12588802 | doi = 10.1093/hmg/ddg049 }}
30. ^{{cite journal | vauthors = Xu J, Wang P, Li Y, Li G, Kaczmarek LK, Wu Y, Koni PA, Flavell RA, Desir GV | title = The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 9 | pages = 3112–7 | date = March 2004 | pmid = 14981264 | pmc = 365752 | doi = 10.1073/pnas.0308450100 }}
31. ^1 {{cite journal | vauthors = Valverde P, Kawai T, Taubman MA | title = Potassium channel-blockers as therapeutic agents to interfere with bone resorption of periodontal disease | journal = Journal of Dental Research | volume = 84 | issue = 6 | pages = 488–99 | date = June 2005 | pmid = 15914584 | doi = 10.1177/154405910508400603 | citeseerx = 10.1.1.327.7276 }}
32. ^{{cite journal | vauthors = Tschritter O, Machicao F, Stefan N, Schäfer S, Weigert C, Staiger H, Spieth C, Häring HU, Fritsche A | title = A new variant in the human Kv1.3 gene is associated with low insulin sensitivity and impaired glucose tolerance | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 91 | issue = 2 | pages = 654–8 | date = February 2006 | pmid = 16317062 | doi = 10.1210/jc.2005-0725 }}
33. ^{{cite journal | vauthors = Rangaraju S, Gearing M, Jin LW, Levey A | title = Potassium channel Kv1.3 is highly expressed by microglia in human Alzheimer's disease | journal = Journal of Alzheimer's Disease | volume = 44 | issue = 3 | pages = 797–808 | date = 2015-02-06 | pmid = 25362031 | pmc = 4402159 | doi = 10.3233/jad-141704 }}
34. ^1 2 {{cite journal | vauthors = Maezawa I, Nguyen HM, Di Lucente J, Jenkins DP, Singh V, Hilt S, Kim K, Rangaraju S, Levey AI, Wulff H, Jin LW | title = Kv1.3 inhibition as a potential microglia-targeted therapy for Alzheimer's disease: preclinical proof of concept | journal = Brain | volume = 141 | issue = 2 | pages = 596–612 | date = February 2018 | pmid = 29272333 | pmc = 5837198 | doi = 10.1093/brain/awx346 }}
35. ^1 {{cite journal | vauthors = Rangaraju S, Dammer EB, Raza SA, Rathakrishnan P, Xiao H, Gao T, Duong DM, Pennington MW, Lah JJ, Seyfried NT, Levey AI | title = Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer's disease | journal = Molecular Neurodegeneration | volume = 13 | issue = 1 | pages = 24 | date = May 2018 | pmid = 29784049 | pmc = 5963076 | doi = 10.1186/s13024-018-0254-8 }}
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42. ^{{cite journal | vauthors = Tudor JE, Pallaghy PK, Pennington MW, Norton RS | title = Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone | journal = Nature Structural Biology | volume = 3 | issue = 4 | pages = 317–20 | date = April 1996 | pmid = 8599755 | doi = 10.1038/nsb0496-317 }}
43. ^{{cite journal | vauthors = Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG | title = ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide | journal = The Journal of Biological Chemistry | volume = 273 | issue = 49 | pages = 32697–707 | date = December 1998 | pmid = 9830012 | doi = 10.1074/jbc.273.49.32697 }}
44. ^{{cite journal | vauthors = Rauer H, Pennington M, Cahalan M, Chandy KG | title = Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 31 | pages = 21885–92 | date = July 1999 | pmid = 10419508 | doi = 10.1074/jbc.274.31.21885 }}
45. ^{{cite journal | vauthors = Han S, Yi H, Yin SJ, Chen ZY, Liu H, Cao ZJ, Wu YL, Li WX | title = Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease | journal = The Journal of Biological Chemistry | volume = 283 | issue = 27 | pages = 19058–65 | date = July 2008 | pmid = 18480054 | doi = 10.1074/jbc.M802054200 }}
46. ^{{cite journal | vauthors = Pennington MW, Beeton C, Galea CA, Smith BJ, Chi V, Monaghan KP, Garcia A, Rangaraju S, Giuffrida A, Plank D, Crossley G, Nugent D, Khaytin I, Lefievre Y, Peshenko I, Dixon C, Chauhan S, Orzel A, Inoue T, Hu X, Moore RV, Norton RS, Chandy KG | title = Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes | journal = Molecular Pharmacology | volume = 75 | issue = 4 | pages = 762–73 | date = April 2009 | pmid = 19122005 | pmc = 2684922 | doi = 10.1124/mol.108.052704 }}
47. ^{{cite journal | vauthors = Cotton J, Crest M, Bouet F, Alessandri N, Gola M, Forest E, Karlsson E, Castañeda O, Harvey AL, Vita C, Ménez A | title = A potassium-channel toxin from the sea anemone Bunodosoma granulifera, an inhibitor for Kv1 channels. Revision of the amino acid sequence, disulfide-bridge assignment, chemical synthesis, and biological activity | journal = European Journal of Biochemistry | volume = 244 | issue = 1 | pages = 192–202 | date = February 1997 | pmid = 9063464 | doi = 10.1111/j.1432-1033.1997.00192.x }}
48. ^{{cite journal | vauthors = Schmitz A, Sankaranarayanan A, Azam P, Schmidt-Lassen K, Homerick D, Hänsel W, Wulff H | title = Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases | journal = Molecular Pharmacology | volume = 68 | issue = 5 | pages = 1254–70 | date = November 2005 | pmid = 16099841 | doi = 10.1124/mol.105.015669 }}
49. ^{{cite journal | vauthors = Zhou YY, Hou GQ, He SW, Xiao Z, Xu HJ, Qiu YT, Jiang S, Zheng H, Li ZY | title = Psora-4, a Kv1.3 Blocker, Enhances Differentiation and Maturation in Neural Progenitor Cells | journal = CNS Neuroscience & Therapeutics | volume = 21 | issue = 7 | pages = 558–67 | date = July 2015 | pmid = 25976092 | doi = 10.1111/cns.12402 }}
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51. ^{{cite journal | vauthors = Miao S, Bao J, Garcia ML, Goulet JL, Hong XJ, Kaczorowski GJ, Kayser F, Koo GC, Kotliar A, Schmalhofer WA, Shah K, Sinclair PJ, Slaughter RS, Springer MS, Staruch MJ, Tsou NN, Wong F, Parsons WH, Rupprecht KM | title = Benzamide derivatives as blockers of Kv1.3 ion channel | journal = Bioorganic & Medicinal Chemistry Letters | volume = 13 | issue = 6 | pages = 1161–4 | date = March 2003 | pmid = 12643934 | doi = 10.1016/S0960-894X(03)00014-3 }}
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53. ^{{cite journal | vauthors = Ehring GR, Kerschbaum HH, Eder C, Neben AL, Fanger CM, Khoury RM, Negulescu PA, Cahalan MD | title = A nongenomic mechanism for progesterone-mediated immunosuppression: inhibition of K + channels, Ca2+ signaling, and gene expression in T lymphocytes | journal = The Journal of Experimental Medicine | volume = 188 | issue = 9 | pages = 1593–602 | date = November 1998 | pmid = 9802971 | pmc = 2212508 | doi = 10.1084/jem.188.9.1593 }}
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58. ^{{cite journal | vauthors = Chuaprapaisilp T, Piamphongsant T | title = Treatment of pustular psoriasis with clofazimine | journal = The British Journal of Dermatology | volume = 99 | issue = 3 | pages = 303–5 | date = September 1978 | pmid = 708598 | doi = 10.1111/j.1365-2133.1978.tb02001.x }}
59. ^{{cite journal | vauthors = Arbiser JL, Moschella SL | title = Clofazimine: a review of its medical uses and mechanisms of action | journal = Journal of the American Academy of Dermatology | volume = 32 | issue = 2 Pt 1 | pages = 241–7 | date = February 1995 | pmid = 7829710 | doi = 10.1016/0190-9622(95)90134-5 }}
60. ^{{cite journal | vauthors = Selby W, Pavli P, Crotty B, Florin T, Radford-Smith G, Gibson P, Mitchell B, Connell W, Read R, Merrett M, Ee H, Hetzel D | title = Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease | journal = Gastroenterology | volume = 132 | issue = 7 | pages = 2313–9 | date = June 2007 | pmid = 17570206 | doi = 10.1053/j.gastro.2007.03.031 }}

External links

  • {{MeshName|KCNA1+protein,+human}}
  • {{MeshName|Kv1.1+Potassium+Channel}}
{{PDB_Gallery|geneid=3738}}{{Ion channels|g3}}{{NLM content}}

1 : Ion channels
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