Glutamate receptor-induced toxicity in neostriatal cells

Infrared differential interference contrast (IR DIC) videomicroscopy was used to measure and characterize cell swelling induced by activation of glutamate receptors (GluR) in a neostriatal brain slice preparation. This swelling is, in many cases, a prelude to necrotic cell death. Activation of N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic GluRs caused cell swelling. The concentration-response relationships and the time courses of the onset of agonist-induced swelling were very similar for NMDA and kainate (KA). However, cells were able to recover from KA but not NMDA-induced swelling. Results from ion substitution experiments suggest that sodium, chloride and to a lesser extent calcium ions play critical roles in this swelling. Heterogeneity in the response to NMDA occurred within cells of the neostriatum. Approximately 15% of the cells did not swell when exposed to NMDA. The magnitude of the NMDA-induced swelling also varied depending on the region of the nervous system. Swelling was greater in the neostriatum and neocortex than in the hippocampus and it did not occur in the suprachiasmatic nucleus. In conclusion, IR DIC videomicroscopy can be used to follow quantitatively the dynamics of GluR-evoked responses in single cells and should be instrumental in determining the factors capable of modifying excitotoxicity.