Ischemic Insults Direct Glutamate Receptor Subunit 2-Lacking AMPA Receptors to Synaptic Sites

• DOI: 10.1523/jneurosci.0567-06.2006
• Publication Date: 2006-05-18T00:19:27Z
• Authors: Baosong Liu; Mingxia Liao; John G. Mielke; Ke Ning; Yonghong Chen; Lei Li; Youssef H. El-Hayek; Everlyne Gomez; R. Suzanne Zukin; Michael G. Fehlings; Qi Wan
• Keywords: Silent synapse; Long-term depression

Regulated AMPA receptor (AMPAR) trafficking at excitatory synapses is a mechanism critical to activity-dependent alterations in synaptic efficacy. The role of regulated AMPAR insult-induced remodeling and/or cell death is, however, as yet unclear. Here we show that brief oxygen–glucose deprivation (OGD), an vitro model brain ischemia, promotes redistribution AMPARs hippocampal neurons, leading switch subunit composition. Ischemic insults promote internalization glutamate 2 (GluR2)-containing from sites via clathrin-dependent endocytosis and facilitate delivery GluR2-lacking soluble N -ethylmaleimide-sensitive factor attachment protein receptor-dependent exocytosis, evident early times after insult. OGD-induced composition requires PKC activation, dissociation GluR2 receptor-binding protein, association with interacting C kinase-1. We further insulted neurons exhibit functional properties AMPARs. AMPAR-mediated miniature EPSCs increased amplitudes enhanced sensitivity subunit-specific blockers AMPARs, 24 h ischemia. currents require clathrin-mediated activation. Thus, ischemic targeting mechanisms may be relevant ischemia-induced neuronal death.