Differentiated Human Midbrain-Derived Neural Progenitor Cells Express Excitatory Strychnine-Sensitive Glycine Receptors Containing α2β Subunits 英文参考文献.docVIP

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Differentiated Human Midbrain-Derived Neural Progenitor Cells Express Excitatory Strychnine-Sensitive Glycine Receptors Containing α2β Subunits 英文参考文献.doc

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Differentiated Human Midbrain-Derived Neural Progenitor Cells Express Excitatory Strychnine-Sensitive Glycine Receptors Containing α2β Subunits 英文参考文献

DifferentiatedHumanMidbrain-DerivedNeural ProgenitorCellsExpressExcitatoryStrychnine-Sensitive GlycineReceptorsContaininga2bSubunits FlorianWegner1*,RobertKraft2,KathyBusse3,WolfgangHa¨rtig4,Jo¨rgAhrens5,AndreasLeffler5, ReinhardDengler1,JohannesSchwarz3 1DepartmentofNeurology,HannoverMedicalSchool,Hannover,Germany,2Carl-Ludwig-InstituteofPhysiology,UniversityofLeipzig,Leipzig,Germany,3Department ofNeurology,UniversityofLeipzig,Leipzig,Germany,4DepartmentofNeurophysiology,PaulFlechsigInstituteofBrainResearch,UniversityofLeipzig,Leipzig,Germany, 5DepartmentofAnaesthesiologyandIntensiveCare,HannoverMedicalSchool,Hannover,Germany Abstract Background:Humanfetalmidbrain-derivedneuralprogenitorcells(NPCs)maydeliveratissuesourcefordrugscreening andregenerativecelltherapytotreatParkinson’sdisease.WhileglutamateandGABAAreceptorsplayanimportantrolein neurogenesis,theinvolvementofglycinereceptorsduringhumanneurogenesisanddopaminergicdifferentiationaswellas theirmolecularandfunctionalcharacteristicsinNPCsarelargelyunknown. Methodology/Principal Findings: Here we investigated NPCs in respect to their glycine receptor function and subunit expression using electrophysiology, calcium imaging, immunocytochemistry, and quantitative real-time PCR. Whole-cell recordingsdemonstratetheabilityofNPCstoexpressfunctionalstrychnine-sensitiveglycinereceptorsafterdifferentiation for 3 weeks in vitro. Pharmacological and molecular analyses indicate a predominance of glycine receptor heteromers containing a2b subunits. Intracellular calcium measurements of differentiated NPCs suggest that glycine evokes depolarisations mediated by strychnine-sensitive glycine receptors and not by D-serine-sensitive excitatory glycine + + receptors. Culturing NPCs with additional glycine, the glycine-receptor antagonist strychnine, or the Na -K -Cl2 co- transporter1(NKCC1)-inhibitorbumetanidedidnotsignificantlyinfluencecellproliferationanddifferentiationinvitro. Conclusions/Significance:ThesedataindicatethatNP