PHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONATE (AMPA) RECEPTORS MEDIATE EXCITOTOXICITY IN THE OLIGODENDROGLIAL LINEAGE

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 rec eptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized ce lls of the rat oligodendroglial lineage express the GlUR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that bo th immortalized and nonimmortalized cells of the oligodendroglial line age are damaged by a 24-h exposure to 500 mu M kainate or 5 mM L-gluta mate, but not by a 24-h exposure to up to 10 mM pha-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NM DA 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 cyt otoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AM PA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca2+-dependent excitotoxicity and that AMPA-i nduced cytotoxicity is blocked by desensitization of AMPA-preferring G luRs.