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dc.contributor.authorZhao, Jerryen
dc.contributor.authorBaudry, Michelen
dc.contributor.authorJones, Susanen
dc.date.accessioned2018-09-05T11:10:35Z
dc.date.available2018-09-05T11:10:35Z
dc.date.issued2018-07en
dc.identifier.issn0028-3908
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279262
dc.description.abstractAbstract Repeated activation of N-Methyl-D-aspartate receptors (NMDARs) causes a Ca2+-dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+-dependent regulatory protein has not been identified. The role of the Ca2+-dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 (‘P7’), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 M) or MDL-28170 (30 M) significantly reduced whole-cell NMDAR current rundown. To investigate the role of the calpain-2 isoform, the membrane permeable calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I, 200 nM), was applied; C2I application significantly reduced whole cell NMDAR current rundown. Interestingly, ALLN but not C2I significantly reduced rundown of NMDA-EPSCs. These results suggest the calpain-2 isoform mediates Ca2+-dependent regulation of extrasynaptic NMDAR current in the first postnatal week, while calpain-1 might mediate rundown of synaptic NMDAR currents. One week later in postnatal development, at P12-P16 (‘P14’), there was significantly less rundown in SNc-DA neurons, and no significant effect on rundown of either Ca2+ chelation or treatment with the calpain inhibitor, ALLN, suggesting that the rundown observed in SNc-DA neurons from two week-old rats might be Ca2+-independent. In conclusion, Ca2+-dependent rundown of extrasynaptic NMDAR currents in SNc DA neurons involves calpain-2 activation, but Ca2+- and calpain-2-dependent NMDAR current rundown is developmentally regulated.
dc.description.sponsorshipNone
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectSynapsesen
dc.subjectAnimalsen
dc.subjectRats, Wistaren
dc.subjectCations, Divalenten
dc.subjectCalciumen
dc.subjectCalpainen
dc.subjectGlycoproteinsen
dc.subjectReceptors, N-Methyl-D-Aspartateen
dc.subjectTissue Culture Techniquesen
dc.subjectMembrane Potentialsen
dc.subjectMembrane Transport Modulatorsen
dc.subjectDopaminergic Neuronsen
dc.subjectPars Compactaen
dc.titleCalpain inhibition reduces NMDA receptor rundown in rat substantia nigra dopamine neurons.en
dc.typeArticle
prism.endingPage229
prism.publicationDate2018en
prism.publicationNameNeuropharmacologyen
prism.startingPage221
prism.volume137en
dc.identifier.doi10.17863/CAM.26642
dcterms.dateAccepted2018-05-02en
rioxxterms.versionofrecord10.1016/j.neuropharm.2018.05.003en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-07en
dc.contributor.orcidBaudry, Michel [0000-0002-5142-241X]
dc.identifier.eissn1873-7064
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2019-05-04


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International