α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage

Akira Yoshioka, Mattie Hardy, Donald P. Younkin, Judith B. Grinspan, Janet L. Stern, David E Pleasure

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 μM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 m/W α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitro-quinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca2+-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Original languageEnglish (US)
Pages (from-to)2442-2448
Number of pages7
JournalJournal of Neurochemistry
Volume64
Issue number6
StatePublished - Jun 1995
Externally publishedYes

Keywords

  • Cyclothiazide
  • Excitotoxicity
  • Kainate
  • Non-NMDA glutamate receptors
  • O-2A cells
  • Oligodendroglia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage'. Together they form a unique fingerprint.

  • Cite this