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Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites.
Liu, Baosong; Liao, Mingxia; Mielke, John G; Ning, Ke; Chen, Yonghong; Li, Lei; El-Hayek, Youssef H; Gomez, Everlyne; Zukin, R Suzanne; Fehlings, Michael G; Wan, Qi.
Afiliação
  • Liu B; Division of Cellular and Molecular Biology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada.
J Neurosci ; 26(20): 5309-19, 2006 May 17.
Article em En | MEDLINE | ID: mdl-16707783
ABSTRACT
Regulated AMPA receptor (AMPAR) trafficking at excitatory synapses is a mechanism critical to activity-dependent alterations in synaptic efficacy. The role of regulated AMPAR trafficking in insult-induced synaptic remodeling and/or cell death is, however, as yet unclear. Here we show that brief oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia, promotes redistribution of AMPARs at synapses of hippocampal neurons, leading to a switch in AMPAR subunit composition. Ischemic insults promote internalization of glutamate receptor subunit 2 (GluR2)-containing AMPARs from synaptic sites via clathrin-dependent endocytosis and facilitate delivery of GluR2-lacking AMPARs to synaptic sites via soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent exocytosis, evident at early times after insult. The OGD-induced switch in receptor subunit composition requires PKC activation, dissociation of GluR2 from AMPA receptor-binding protein, and association with protein interacting with C kinase-1. We further show that AMPARs at synapses of insulted neurons exhibit functional properties of GluR2-lacking AMPARs. AMPAR-mediated miniature EPSCs exhibit increased amplitudes and enhanced sensitivity to subunit-specific blockers of GluR2-lacking AMPARs, evident at 24 h after ischemia. The OGD-induced alterations in synaptic AMPA currents require clathrin-mediated receptor endocytosis and PKC activation. Thus, ischemic insults promote targeting of GluR2-lacking AMPARs to synapses of hippocampal neurons, mechanisms that may be relevant to ischemia-induced synaptic remodeling and/or neuronal death.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Encéfalo / Receptores de AMPA / Transmissão Sináptica / Hipóxia-Isquemia Encefálica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sinapses / Encéfalo / Receptores de AMPA / Transmissão Sináptica / Hipóxia-Isquemia Encefálica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Neurosci Ano de publicação: 2006 Tipo de documento: Article País de afiliação: Canadá