Recent studies indicate that oligodendrocytes are vulnerable to excitotoxic insults mediated by glutamate receptors. The present study was carried out to characterize the type of glutamate receptors triggering cell death in optic nerve oligodendrocyte cultures. Acute activation of either AMPA or kainate receptors was toxic to oligodendrocytes, an effect that was prevented by CNQX. However, exposure to agonists of the NMDA and metabotropic glutamate receptors did not impair cell viability. Dose-response curves showed that toxicity was mediated by three distinct populations of receptors: an AMPA-type receptor and high- and low-affinity kainate-type receptors. Expression and immunocytochemical studies suggested that the glutamate receptor subunits give rise to the native receptors in each population. In all instances, Ca(2+) entry was a major determinant of glutamate receptor excitotoxicity. However, its influence varied for each receptor subtype. These results indicate that aberrantly enhanced activation of AMPA and/or kainate receptors may be involved in demyelinating diseases.
Copyright 1999 Academic Press.