| 词条 | SK3 |
| 释义 |
SK3 is a small-conductance calcium-activated potassium channel partly responsible for the calcium-dependent after hyperpolarisation current (IAHP). It belongs to a family of channels known as small-conductance potassium channels, which consists of three members – SK1, SK2 and SK3 (encoded by the KCNN1, 2 and 3 genes respectively), which share a 60-70% sequence identity.[3] These channels have acquired a number of alternative names, however a NC-IUPHAR has recently achieved consensus on the best names, KCa2.1 (SK1), KCa2.2 (SK2) and KCa2.3 (SK3).[2] Small conductance channels are responsible for the medium and possibly the slow components of the IAHP. StructureKCa2.3 contains 6 transmembrane domains, a pore-forming region, and intracellular N- and C- termini[3][4] and is readily blocked by apamin. The gene for KCa2.3, KCNN3, is located on chromosome 1q21. ExpressionKCa2.3 is found in the central nervous system (CNS), muscle, liver, pituitary, prostate, kidney, pancreas and vascular endothelium tissues.[5] KCa2.3 is most abundant in regions of the brain, but has also been found to be expressed in significant levels in many other peripheral tissues, particularly those rich in smooth muscle, including the rectum, corpus cavernosum, colon, small intestine and myometrium.[3] The expression level of KCNN3 is dependent on hormonal regulation, particularly by the sex hormone estrogen. Estrogen not only enhances transcription of the KCNN3 gene, but also affects the activity of KCa2.3 channels on the cell membrane. In GABAergic preoptic area neurons, estrogen enhanced the ability of α1 adrenergic receptors to inhibit KCa2.3 activity, increasing cell excitability.[6] Links between hormonal regulation of sex organ function and KCa2.3 expression have been established. The expression of KCa2.3 in the corpus cavernosum in patients undergoing estrogen treatment as part of gender reassignment surgery was found to be increased up to 5-fold.[3] The influence of estrogen on KCa2.3 has also been established in the hypothalamus, uterine and skeletal muscle.[6] PhysiologyKCa2.3 channels play a major role in human physiology, particularly in smooth muscle relaxation. The expression level of KCa2.3 channels in the endothelium influences arterial tone by setting arterial smooth muscle membrane potential. The sustained activity of KCa2.3 channels induces a sustained hyperpolarisation of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions.[7] Blocking the KCa2.3 channel or suppressing KCa2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance and blood pressure. PathologyMutations in KCa2.3 are suspected to be a possible underlying cause for several neurological disorders, including schizophrenia, bipolar disorder, Alzheimer's disease, anorexia nervosa and ataxia[8][9][10] as well as myotonic muscular dystrophy.[11]References1. ^{{cite journal | vauthors = Chandy KG, Fantino E, Wittekindt O, Kalman K, Tong LL, Ho TH, Gutman GA, Crocq MA, Ganguli R, Nimgaonkar V, Morris-Rosendahl DJ, Gargus JJ | title = Isolation of a novel potassium channel gene hSKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia and bipolar disorder? | journal = Mol. Psychiatry | volume = 3 | issue = 1 | pages = 32–7 |date=January 1998 | pmid = 9491810 | doi = 10.1038/sj.mp.4000353}} 2. ^1 {{cite journal | vauthors = Wei AD, Gutman GA, Aldrich R, Chandy KG, Grissmer S, Wulff H | title = International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels | journal = Pharmacol. Rev. | volume = 57 | issue = 4 | pages = 463–72 |date=December 2005 | pmid = 16382103 | doi = 10.1124/pr.57.4.9 }} 3. ^1 2 3 {{cite journal | vauthors = Chen MX, Gorman SA, Benson B, Singh K, Hieble JP, Michel MC, Tate SN, Trezise DJ | title = Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum | journal = Naunyn Schmiedebergs Arch. Pharmacol. | volume = 369 | issue = 6 | pages = 602–15 |date=June 2004 | pmid = 15127180 | doi = 10.1007/s00210-004-0934-5 }} 4. ^{{cite journal | vauthors = Köhler M, Hirschberg B, Bond CT, Kinzie JM, Marrion NV, Maylie J, Adelman JP | title = Small-conductance, calcium-activated potassium channels from mammalian brain | journal = Science | volume = 273 | issue = 5282 | pages = 1709–14 |date=September 1996 | pmid = 8781233 | doi = 10.1126/science.273.5282.1709 }} 5. ^{{cite journal | vauthors = Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V | title = Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications | journal = Curr. Med. Chem. | volume = 14 | issue = 13 | pages = 1437–57 | year = 2007 | pmid = 17584055 | doi = 10.2174/092986707780831186 }} 6. ^1 {{cite journal | vauthors = Jacobson D, Pribnow D, Herson PS, Maylie J, Adelman JP | title = Determinants contributing to estrogen-regulated expression of SK3 | journal = Biochem. Biophys. Res. Commun. | volume = 303 | issue = 2 | pages = 660–8 |date=April 2003 | pmid = 12659870 | doi = 10.1016/S0006-291X(03)00408-X| url = }} 7. ^{{cite journal | vauthors = Taylor MS, Bonev AD, Gross TP, Eckman DM, Brayden JE, Bond CT, Adelman JP, Nelson MT | title = Altered expression of small-conductance Ca2+-activated K+ (SK3) channels modulates arterial tone and blood pressure | journal = Circ. Res. | volume = 93 | issue = 2 | pages = 124–31 |date=July 2003 | pmid = 12805243 | doi = 10.1161/01.RES.0000081980.63146.69 }} 8. ^{{cite journal | vauthors = Koronyo-Hamaoui M, Gak E, Stein D, Frisch A, Danziger Y, Leor S, Michaelovsky E, Laufer N, Carel C, Fennig S, Mimouni M, Apter A, Goldman B, Barkai G, Weizman A | title = CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population | journal = Am. J. Med. Genet. B Neuropsychiatr. Genet. | volume = 131B | issue = 1 | pages = 76–80 |date=November 2004 | pmid = 15389773 | doi = 10.1002/ajmg.b.20154 }} 9. ^{{cite journal | vauthors = Koronyo-Hamaoui M, Frisch A, Stein D, Denziger Y, Leor S, Michaelovsky E, Laufer N, Carel C, Fennig S, Mimouni M, Ram A, Zubery E, Jeczmien P, Apter A, Weizman A, Gak E | title = Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa | journal = J Psychiatr Res | volume = 41 | issue = 1–2 | pages = 160–7 | year = 2007 | pmid = 16157352 | doi = 10.1016/j.jpsychires.2005.07.010 }} 10. ^{{cite journal | vauthors = Tomita H, Shakkottai VG, Gutman GA, Sun G, Bunney WE, Cahalan MD, Chandy KG, Gargus JJ | title = Novel truncated isoform of SK3 potassium channel is a potent dominant-negative regulator of SK currents: implications in schizophrenia | journal = Mol. Psychiatry | volume = 8 | issue = 5 | pages = 524–35, 460 |date=May 2003 | pmid = 12808432 | doi = 10.1038/sj.mp.4001271 }} 11. ^{{cite journal | vauthors = Kimura T, Takahashi MP, Fujimura H, Sakoda S | title = Expression and distribution of a small-conductance calcium-activated potassium channel (SK3) protein in skeletal muscles from myotonic muscular dystrophy patients and congenital myotonic mice | journal = Neurosci. Lett. | volume = 347 | issue = 3 | pages = 191–5 |date=August 2003 | pmid = 12875918 | doi = 10.1016/S0304-3940(03)00638-4| url = }} Further reading{{refbegin|35em}}
2 : Neurochemistry|Ion channels |
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