Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites

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

Research output: Contribution to journalArticle

120 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5309-5319
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number20
DOIs
StatePublished - 2006

Fingerprint

AMPA Receptors
Glutamate Receptors
Synapses
Clathrin
Oxygen
Endocytosis
Neurons
Glucose
Ischemia
SNARE Proteins
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neuronal Plasticity
Exocytosis
Brain Ischemia
(2-azidomethyl)phenylacetyl
Carrier Proteins
Cell Death
Phosphotransferases
Proteins

Keywords

  • AMPA receptors
  • GluR2 subunit
  • Ischemia
  • Neuronal death
  • Receptor trafficking
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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.

In: Journal of Neuroscience, Vol. 26, No. 20, 2006, p. 5309-5319.

Research output: Contribution to journalArticle

Liu, B, Liao, M, Mielke, JG, Ning, K, Chen, Y, Li, L, El-Hayek, YH, Gomez, E, Zukin, RS, Fehlings, MG & Wan, Q 2006, 'Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites', Journal of Neuroscience, vol. 26, no. 20, pp. 5309-5319. https://doi.org/10.1523/JNEUROSCI.0567-06.2006
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. / Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 20. pp. 5309-5319.
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AU - Li, Lei

AU - El-Hayek, Youssef H.

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