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

J Neurochem. 1995 Jun;64(6):2442-8. doi: 10.1046/j.1471-4159.1995.64062442.x.


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 microM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 mM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitroquinoxaline-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 Ca(2+)-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Gene Expression
  • Glutamic Acid / pharmacology
  • Ion Channels / genetics
  • Kainic Acid / pharmacology
  • Molecular Sequence Data
  • Neurotoxins / pharmacology*
  • Oligodendroglia / drug effects*
  • Oligonucleotide Probes / genetics
  • Polymerase Chain Reaction
  • Rats
  • Receptors, AMPA / physiology*
  • Receptors, Glutamate / metabolism
  • Transcription, Genetic
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Ion Channels
  • Neurotoxins
  • Oligonucleotide Probes
  • Receptors, AMPA
  • Receptors, Glutamate
  • Glutamic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Kainic Acid