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Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A2A receptors

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dc.contributor.authorDias, Raquel B.
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2012-05-30T11:50:30Z
dc.date.available2012-05-30T11:50:30Z
dc.date.issued2012
dc.descriptionCopyright © 2010 Wiley Periodicals, Inc.por
dc.description[The definitive version is available at www3.interscience.wiley.com] [A versão definitiva está disponível em www3.interscience.wiley.com]eng
dc.description.abstractPhosphorylation of glutamate -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors by Protein Kinase A (PKA) is known to regulate AMPA receptor (AMPAR) trafficking and stabilization at the postsynaptic membrane, which in turn is one of the key mechanisms by which synaptic transmission and plasticity are tuned. However, not much is known as to how Gs-coupled receptors contribute to endogenous PKA-mediated regulation of AMPA receptor function. Here we report that activation of the excitatory A2A adenosine receptor by 2-[4-(2-p-carboxyethyl)phenylamino]-5′-N-ethylcarboxamidoadenosine (CGS 21680, 1–30 nM) facilitates AMPA-evoked currents in CA1 pyramidal neurons, by a mechanism dependent on PKA activation, but not on protein synthesis. This modulation of AMPA currents was mimicked by forskolin (1 μM) and did not occur in stratum radiatum interneurons. Superfusion of the A2A receptor agonist also caused an increase in the amplitude of miniature excitatory postsynaptic currents (mEPSCs), as well as in the membrane levels of GluR1 subunits phosphorylated at the PKA site (Ser845). The impact of this increase on GluR1-containing AMPA receptor expression was evidenced by the potentiation of LTP at the CA3-CA1 synapse that followed brief activation of A2A receptors. We thus propose that in conditions of increased adenosine availability, A2A receptor activation is responsible for setting part of the endogenous GluR1 Ser-845 phosphorylation tonus and hence, the availability of the GluR1-containing AMPA receptor extrasynaptic pool for synaptic insertion and reinforcement of synaptic strength.eng
dc.description.sponsorshipFunded by FCT, EU; Grant numbers: SFRH/BD/27761/2006; PTDC/SAU-FCF7168607/2006; Cost B30.eng
dc.identifier.citationHIPPOCAMPUS 22:276–291 (2012)por
dc.identifier.issn1050-9631
dc.identifier.urihttp://hdl.handle.net/10451/6388
dc.identifier.uriDOI 10.1002/hipo.20894
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherWiley-Blackwellpor
dc.subjectGs-coupled receptorseng
dc.subjectHippocampuseng
dc.subjectSynaptic plasticityeng
dc.subjectPostsynaptic AMPA functioneng
dc.subjectCA1 pyramidal neuronseng
dc.titleEnhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A2A receptorseng
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage291por
oaire.citation.startPage276por
oaire.citation.titleHippocampuspor
person.familyNameRibeiro
person.familyNameSebastião
person.givenNameJoaquim
person.givenNameAna M
person.identifier.ciencia-id081F-2518-907F
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0002-9330-3507
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id35498669400
person.identifier.scopus-author-id7004409879
rcaap.rightsrestrictedAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublication86da944c-5e6a-4ec5-a56e-4ed82ece7a17
relation.isAuthorOfPublication304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isAuthorOfPublication.latestForDiscovery304abd7f-071b-4447-a8a3-4aa5f0547141

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