AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes

Takayuki Ito, Jacqueline Beesley, Aki Itoh, Akiva S. Cohen, Bryan Kavanaugh, Douglas A. Coulter, Judith B. Grinspan, David E Pleasure

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Cells of the oligodendroglial lineage express Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-preferring glutamate receptors (AMPA-GluR) during development. Prolonged activation of their AMPA-GluR causes Ca2+ overload, resulting in excitotoxic death. Prior studies have shown that oligodendroglial progenitors and immature oligodendrocytes are susceptible to excitotoxicity, whereas mature oligodendrocytes are resistant. An unresolved issue has been why Ca2+-permeability of AMPA-GluR varies so markedly with oligodendroglial development, although the level of expression of edited GluR2, an AMPA-GluR subunit which blocks Ca2+ entry, is relatively constant. To address this question, we performed Ca2+ imaging, molecular and electrophysiological analyses using purified cultures of the rat oligodendroglial lineage. We demonstrate that transient up-regulation of expression of GluR3 and GluR4 subunits in oligodendroglial progenitors and immature oligodendrocytes results in the assembly by these cells, but not by oligodendroglial pre-progenitors or mature oligodendrocytes, of a population of AMPA-GluR which lack GluR2. This stage-specific up-regulation of edited GluR2-free, and hence Ca2+-permeable, AMPA-GluR explains the selective susceptibility to excitotoxicity of cells at these stages of oligodendroglial differentiation, and is likely to be important to these cells in the trans-synaptic Ca2+-signaling from glutamatergic neurons, which occurs in hippocampus in vivo.

Original languageEnglish (US)
Pages (from-to)390-402
Number of pages13
JournalJournal of Neurochemistry
Volume81
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • AMPA receptor
  • Calcium
  • Electrophysiology
  • Fura-2 microfluorometry
  • Oligodendroglial lineage

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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