Fast Inhibition of Glutamate-Activated Currents by Caffeine 英文参考文献.docVIP

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Fast Inhibition of Glutamate-Activated Currents by Caffeine 英文参考文献.doc

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Fast Inhibition of Glutamate-Activated Currents by Caffeine 英文参考文献

FastInhibitionofGlutamate-ActivatedCurrentsby Caffeine NicholasP.Vyleta,StephenM.Smith* DivisionofPulmonaryCriticalCareMedicine,OregonHealthScienceUniversity,Portland,Oregon,UnitedStatesofAmerica Abstract Background:Caffeinestimulatescalcium-inducedcalciumrelease(CICR)inmanycelltypes.Inneurons,caffeinestimulates CICRpresynapticallyandthusmodulatesneurotransmitterrelease. Methodology/PrincipalFindings:Usingthewhole-cellpatch-clamptechniquewefoundthatcaffeine(20mM)reversibly increasedthefrequencyanddecreasedtheamplitudeofminiatureexcitatorypostsynapticcurrents(mEPSCs)inneocortical neurons.TheincreaseinmEPSCfrequencyisconsistentwithapresynapticmechanism.Caffeinealsoreducedexogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds,consistentwithblockofchannelcurrents.Caffeine(20mM)didnotreducecurrentsactivatedbyexogenous NMDA,indicatingthatcaffeineblockisspecifictonon-NMDAtypeglutamatereceptors. Conclusions/Significance: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non- NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses. Citation:VyletaNP,SmithSM(2008)FastInhibitionofGlutamate-ActivatedCurrentsbyCaffeine.PLoSONE3(9):e3155.doi:10.1371/journal.pone.0003155 Editor:EshelBen-Jacob,TelAvivUniversity,Israel ReceivedMay13,2008;AcceptedAugust18,2008;PublishedSeptember10,2008 Copyright: ? 2008 Vyleta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyNINDS(R01-NS43444)andMultidisciplinaryResearchTraininginPulmonaryMedicineTrainingGrant(1T32HL083808). CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:smisteph@ Introduction Results Thepopularstimulant,ca