Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals 英文参考文献.docVIP

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Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals 英文参考文献.doc

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Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals 英文参考文献

PresynapticExternalCalciumSignalingInvolvesthe Calcium-SensingReceptorinNeocorticalNerve Terminals WenyanChen1,JeremyB.Bergsman1,XiaohuaWang1,GawainGilkey1,Carol-Rene′ePierpoint1,ErinA. Daniel1,EmmanuelM.Awumey2,PhilippeDauban3,RobertH.Dodd3,MartialRuat4,StephenM.Smith1* 1Division of Pulmonary Critical Care Medicine, Oregon Health Science University, Portland, Oregon, United States of America, 2Julius L. Chambers Biomedical/ BiotechnologyResearchInstitute,NorthCarolinaCentralUniversity,Durham,NorthCarolina,UnitedStatesofAmerica, 3CentreNationaldelaRechercheScientifique, Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France, 4Centre National de la Recherche Scientifique, Institut de Neurobiologie Alfred Fessard, Gif-sur- Yvette,France Abstract Background:Nerveterminalinvasionbyanaxonalspikeactivatesvoltage-gatedchannels,triggeringcalciumentry,vesicle fusion,andreleaseofneurotransmitter.Ionchannelsactivatedattheterminalshapethepresynapticspikeandsoregulate themagnitudeanddurationofcalciumentry.Consequentlycharacterizationofthefunctionalpropertiesofionchannelsat nerveterminalsiscrucialtounderstandtheregulationoftransmitterrelease.Directrecordingsfromsmallneocorticalnerve 2+ 2+ terminals have revealed that external [Ca ] ([Ca ]o) indirectly regulates a non-selective cation channel (NSCC) in 2+ neocorticalnerveterminalsviaanunknown[Ca ]osensor.Here,weidentifythefirstcomponentinapresynapticcalcium signalingpathway. Methodology/Principal Findings: By combining genetic and pharmacological approaches with direct patch-clamp recordingsfromsmallacutelyisolatedneocorticalnerveterminalsweidentifytheextracellularcalciumsensor.Ourresults showthatthecalcium-sensingreceptor(CaSR),apreviouslyidentifiedG-proteincoupledreceptorthatisthemainstayin serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC 2+ currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca ]o than