This article is about the human protein3. For the Finnish Steam Locomotive, seeVR Class Sk3. For SK-3, the Russian spaceport, seePlesetsk Cosmodrome Site 43. For the 1930s air racer, seeFolkerts SK-3. For SK3, the U.S Navy rate and rank, seeStorekeeper.
SK3 (small conductance calcium-activated potassium channel 3) also known asKCa2.3 is aprotein that in humans is encoded by theKCNN3gene.[5][6]
SK3 is a small-conductancecalcium-activated potassium channel partly responsible for thecalcium-dependentafter hyperpolarisation current (IAHP). It belongs to a family of channels known assmall-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.[7] 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) andKCa2.3 (SK3).[6] Small conductance channels are responsible for the medium and possibly the slow components of the IAHP.
Theexpression level of KCNN3 is dependent onhormonal regulation, particularly by thesex hormoneestrogen. Estrogen not only enhancestranscription of the KCNN3 gene, but also affects the activity of KCa2.3 channels on thecell membrane. InGABAergicpreoptic area neurons, estrogen enhanced the ability ofα1 adrenergic receptors to inhibit KCa2.3 activity, increasing cell excitability.[10] Links between hormonal regulation ofsex 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 ofgender reassignment surgery was found to be increased up to 5-fold.[7] The influence of estrogen on KCa2.3 has also been established in thehypothalamus,uterine andskeletal muscle.[10]
KCa2.3 channels play a major role in human physiology, particularly insmooth muscle relaxation. The expression level of KCa2.3 channels in theendothelium influencesarterial tone by setting arterial smooth musclemembrane potential. The sustained activity of KCa2.3 channels induces a sustainedhyperpolarisation of the endothelial cell membrane potential, which is then carried to nearby smooth muscle through gap junctions.[11] Blocking the KCa2.3 channel or suppressing KCa2.3 expression causes a greatly increased tone in resistance arteries, producing an increase in peripheral resistance andblood pressure.
^abcdChen MX, Gorman SA, Benson B, Singh K, Hieble JP, Michel MC, Tate SN, Trezise DJ (June 2004). "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".Naunyn-Schmiedeberg's Arch. Pharmacol.369 (6):602–15.doi:10.1007/s00210-004-0934-5.PMID15127180.S2CID6309146.
^Wulff H, Kolski-Andreaco A, Sankaranarayanan A, Sabatier JM, Shakkottai V (2007). "Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications".Curr. Med. Chem.14 (13):1437–57.doi:10.2174/092986707780831186.PMID17584055.S2CID13139192.
^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 (November 2004). "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".Am. J. Med. Genet. B Neuropsychiatr. Genet.131B (1):76–80.doi:10.1002/ajmg.b.20154.PMID15389773.S2CID24415070.
^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 (2007). "Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa".J Psychiatr Res.41 (1–2):160–7.doi:10.1016/j.jpsychires.2005.07.010.PMID16157352.
^Kimura T, Takahashi MP, Fujimura H, Sakoda S (August 2003). "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".Neurosci. Lett.347 (3):191–5.doi:10.1016/S0304-3940(03)00638-4.PMID12875918.S2CID11678544.
Glatt SJ, Faraone SV, Tsuang MT (2003). "CAG-repeat length in exon 1 of KCNN3 does not influence risk for schizophrenia or bipolar disorder: a meta-analysis of association studies".Am. J. Med. Genet. B Neuropsychiatr. Genet.121B (1):14–20.doi:10.1002/ajmg.b.20048.PMID12898569.S2CID7397950.
Ivković M, Ranković V, Tarasjev A, et al. (2006). "Schizophrenia and polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene in Serbian population".Int. J. Neurosci.116 (2):157–64.doi:10.1080/00207450341514.PMID16393881.S2CID31789520.
Decimo I, Roncarati R, Grasso S, et al. (2006). "SK3 trafficking in hippocampal cells: the role of different molecular domains".Biosci. Rep.26 (6):399–412.doi:10.1007/s10540-006-9029-5.PMID17061167.S2CID38653604.
Laurent C, Niehaus D, Bauché S, et al. (2003). "CAG repeat polymorphisms in KCNN3 (HSKCa3) and PPP2R2B show no association or linkage to schizophrenia".Am. J. Med. Genet. B Neuropsychiatr. Genet.116B (1):45–50.doi:10.1002/ajmg.b.10797.PMID12497613.S2CID20643826.
Ritsner M, Amir S, Koronyo-Hamaoui M, et al. (2003). "Association study of CAG repeats in the KCNN3 gene in Israeli patients with major psychosis".Psychiatr. Genet.13 (3):143–50.doi:10.1097/00041444-200309000-00002.PMID12960745.S2CID11378997.
Zhou Z, Jiang DJ, Jia SJ, et al. (2007). "Down-regulation of endogenous nitric oxide synthase inhibitors on endothelial SK3 expression".Vascul. Pharmacol.47 (5–6):265–71.doi:10.1016/j.vph.2007.08.003.PMID17869187.
Koronyo-Hamaoui M, Gak E, Stein D, et al. (2004). "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".Am. J. Med. Genet. B Neuropsychiatr. Genet.131B (1):76–80.doi:10.1002/ajmg.b.20154.PMID15389773.S2CID24415070.
Piotrowska AP, Solari V, Puri P (2003). "Distribution of Ca2+-activated K channels, SK2 and SK3, in the normal and Hirschsprung's disease bowel".J. Pediatr. Surg.38 (6):978–83.doi:10.1016/S0022-3468(03)00138-6.PMID12778407.
Hong XH, Xu CT, Yang Q, Wu CR (2005). "[Transmission disequilibrium analysis of 1137-1140 Del GTGA frameshift mutation within the KCNN3 gene and schizophrenia based on family trios]".Zhonghua Yi Xue Yi Chuan Xue Za Zhi.22 (4):441–3.PMID16086287.
