AMPA and kainate receptors each mediate excitotoxicity in oligodendroglialcultures

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 o ptic nerve oligodendrocyte cultures. Acute activation of either AM PA or ka inate receptors was toxic to oligodendrocytes, an effect that was prevented by CNQX. However, exposure to agonists of the NMDA and metabotropic glutam ate receptors did not impair cell viability. Dose-response curves showed th at toxicity was mediated by three distinct populations of receptors: an AMP A-type receptor and high- and low-affinity kainate-type receptors. Expressi on and immunocytochemical studies suggested that the glutamate receptor sub units give rise to the native receptors in each population. In all instance s, Ca2+ entry was a major determinant of glutamate receptor excitotoxicity. However, its influence varied for each receptor subtype. These results ind icate that aberrantly enhanced activation of AMPA and/or kainate receptors may be involved in demyelinating diseases. (C) 1999 Academic Press.