Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/6388
Título: Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A2A receptors
Autor: Dias, Raquel B.
Ribeiro, Joaquim A.
Sebastião, Ana M.
Palavras-chave: Gs-coupled receptors
Synaptic plasticity
Postsynaptic AMPA function
CA1 pyramidal neurons
Data: 2012
Editora: Wiley-Blackwell
Citação: HIPPOCAMPUS 22:276–291 (2012)
Resumo: Phosphorylation 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.
Descrição: Copyright © 2010 Wiley Periodicals, Inc.
[The definitive version is available at www3.interscience.wiley.com] [A versão definitiva está disponível em www3.interscience.wiley.com]
Peer review: yes
URI: http://hdl.handle.net/10451/6388
DOI 10.1002/hipo.20894
ISSN: 1050-9631
Aparece nas colecções:FM-IFN-Artigos em Revistas Internacionais

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