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1、http://www.paper.edu.cn2+InhibitoryeffectofCdonglycinereceptorsinrathippocampalneuronsWangShuRuanDi-Yun*wangshu@mail.ustc.edu.cnRuandy@ustc.edu.cnSchoolofLifeScience,UniversityofScience&TechnologyofChina,Hefei,Anhui230027,P.R.ChinaAbstract2+－Theeffectsofcad
2、mium(Cd)onglycine-inducedClcurrent(IGly)wereinvestigatedinacutelydissociatedrathippocampalCA1neuronsusingthe2+conventionalwhole-cellpatch-clamptechniqueinthisstudy.WefoundthatCdreversiblyandconcentration-dependentlyreducedtheamplitudesofIGly,withanIC502+of1
3、.27mMandHillcoefficientof0.45.ThedepressionofIGlybyCdwasindependentofmembranevoltagebetween-60mVand+40mVanddidn’tinvolveashiftinthereversalpotentialofthecurrent.Anoncompetitiveinhibitionwassuggested2+byadoublereciprocalplotoftheeffectsofCdontheconcentration
4、-responsecurveof2+theIGly.Sinceintracellulardialysiswith3mMCdfailedtomodifyIGly,itwas2+2+suggestedthatthesiteofactionofCdisextracellular.ThesuppressionofIGlybyZn2+2+2+wasunaffectedby3mMCd,whichindicatedthatZnandCdbindtoindependent2+sitesonglycinereceptor.Th
5、eresultsshowthatCddecreasesIGlyinacutely2+dissociatedrathippocampalneuronsandthedepressionofIGlybyCdmaycontributetoworsentheneurotoxicologicalimpairment.KeyWords2+:Cd;glycinereceptor;whole-cellrecording;hippocampalneuron;neurotoxicity*CorrespondingAuthor:Th
6、isworkwassupportedbyTheNationalBasicResearchProgramofChina(No.2002CB512907),AcademiaSinica(No.KZCX3-SW-437，KZCX3-SW-151),TheNationalNatureScienceFoundationofChina(No.40231002;30300288,30170809;),SpecializedResearchFundfortheDoctoralProgramofHigherEducation(
7、No.20020358053),1http://www.paper.edu.cn1.IntroductionCadmium，apollutantfoundintheenvironment,iswellknownforitspotentiallytoxictohuman.Cadmiumhasalongbiologicalhalf-life(over15yearsinhumans)andchronicexposurecausescarcinogenic,mutagenicandteratogeniceffects
8、,damagingofmultipleorgans,includingthekidney,lung,gastrointestinaltract,boneandalsothebrain[12,19,21,25,34].Thebrainisatargetforcadmiumtoxicity,especiallyduringdevelopment.Numerousanimalstudieshavedemo
