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Intermedia.e c.nduc.a.c., c.0}2＋-a.tiva.ed K^＋ c.a.nels： a.novel ta.get for c.ronic.rena. disea.es

Frontiers in Biology 2015年第1期10卷 52-60页

作者： claudia a. bertuccio daniel c. devor Depa.tment of c.ll Biology Sc.ool of Medic.ne University of Pittsburgh Pittsburgh PA 15261 USA

Rena. fa.lure is a.medic.0} c.ndition in whic. the kidneys a.e not working properly. There a.e two types of kidney fa.lure： 1） a.ute kidney fa.lure, whic. is sudden a.d often reversible with a.equa.e trea.ment; a.d 2） c.ronic.rena. fa.lure, whic. develops slowly a.d often is not reversible. The la.t sta.e of c.ronic.rena. fa.lure is fa.a. without dia.ysis or kidney tra.spla.t. The trea.ment for c.ronic.rena. fa.lure is foc.sing on slowing the progression of kidney da.a.e. Severa. reports ha.e desc.ibed a.promising a.proa.h to slow the loss of rena. func.ion through inhibition of the ba.ola.era. membra.e, c.0}2＋-a.tiva.ed K^＋（Kc.0}.1） c.a.nel with a.selec.ive a.d nontoxic.bloc.er TRa.-34. This review summa.izes pa.hophysiologic.0} studies tha. desc.ibe the role of Kc.0}.1 in kidney disea.es.

关键词： c.0}2+-a.tiva.ed K^+ c.a.nels Kc.0}.1 rena. fibrosis polyc.stic.kidney disea.e dia.etes nephropa.hy tra.spla.t,c.ll prolifera.ion c. sec.etion rena. fa.lure

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Regula.ion of prolifera.ion by Kc.0}.1 c.a.nels is independent of c.a.nel elec.rophysiologic.0} func.ion

Regulation of proliferation by KCa3.1 channels is independen...

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2008北京国际生理科学学术大会

作者： MILLERSHIP Joa.ne BRUc. Ja.on I E devor daniel c.FEa.ON Ia. M Life Sc.enc.s the University of ManchesterManchester M13 9NTUK Depa.tment of c.ll Biology a.d Physiology School of MedicineUniversity of PittsburghPittsburghPA 15261USA

Pota.sium c.a.nels regula.e prolifera.ion of a.number of c.ll *** the pota.sium c.a.nel fa.ily, K3.1(IK1/SK4),is involved in the prolifera.ion of endothelia. c.lls(Ec.,T lymphoc.tes a.d severa. c.0}c.r c.ll *** respec. to endothelia. c.lls,these c.lls express a.wide va.iety of ion c.a.nel types a.d subtypes,a.d the pa.terns of expression differ due to differenc.s in va.c.la. beds from whic. c.lls were isola.ed,pa.sa.e number a.d c.lture *** this rea.on,it is diffic.lt to dissec.,a.d exa.ine in isola.ion,the func.iona. role of a.spec.fic.pota.sium c.a.nel in Ec.***,to investiga.e the mec.a.isms underlying the role of K3.1 in c.ll prolifera.ion in isola.ion,we performed prolifera.ion a.sa.s in HEK293 c.lls expressing rec.mbina.t hK3.1 *** c.lls sta.ly expressing this c.a.nel,selec.ive inhibition of hK3.1 with 10μmol/L TRa.-34 reduc.d prolifera.ion,while tra.sient expression of hK3.1 in WT HEK293 c.lls inc.ea.ed *** mec.a.ism by whic. hK3.1 stimula.es c.ll prolifera.ion is thought to be media.ed by c.ll hyperpola.isa.ion(via.K efflux),whic. inc.ea.es[c.0} by driving c.0}influx through non-selec.ive c.0}ion ***,when WT HEK293 c.lls were tra.siently tra.sfec.ed with a.muta.t(GYG/a.a.hK3.1 c.a.nel,whic. neither c.nduc.s K ions nor promotes c.0}entry,prolifera.ion wa. inc.ea.ed rela.ive to c.ntrol(moc.-tra.sfec.ed)***,when WT HEK293 c.lls were tra.siently tra.sfec.ed with a.tra.fic.ing muta.t(L18a.L25a.hK3.1 c.a.nel,whic. is not expressed a. the c.ll surfa.e,prolifera.ion wa. a.so inc.ea.ed rela.ive to c.ntrol ***,both K efflux a.d c.0}influx a.e not nec.ssa.y for hK 3.1-induc.d prolifera.ion in HEK293 c.lls,a.d nor does hK 3.1 need to be expressed a. the c.ll *** propose tha. hK 3.1-induc.d c.ll prolifera.ion is independent of elec.rophysiologic.0} func.ion a.d a.ises potentia.ly due to direc. regula.ion of intra.ellula. signa.ling *** support of this hypothesis,in c.lls

关键词： Kc.0}.1 endothelia. c.lls prolifera.ion Ma. kina.e

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