GLUTAMATE RECEPTOR-INDUCED TOXICITY IN NEOSTRIATAL CELLS

Infrared differential interference contrast (IR DIG) videomicroscopy w as used to measure and characterize cell swelling induced by activatio n of glutamate receptors (GluR) in a neostriatal brain slice preparati on. This swelling is, in many cases, a prelude to necrotic cell death. Activation of N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic Glu Rs caused cell swelling. The concentration-response relationships and the time courses of the onset of agonist-induced swelling were very si milar for NMDA and kainate (KA). However, cells were able to recover f rom KA but not NMDA-induced swelling. Results from ion substitution ex periments suggest that sodium, chloride and to a lesser extent calcium ions play critical roles in this swelling. Heterogeneity in the respo nse to NMDA occurred within cells of the neostriatum. Approximately 15 % of the cells did not swell when exposed to NMDA. The magnitude of th e NMDA-induced swelling also varied depending on the region of the ner vous system. Swelling was greater in the neostriatum and neocortex tha n in the hippocampus and it did not occur in the suprachiasmatic nucle us. In conclusion, IR DIC videomicroscopy can be used to follow quanti tatively the dynamics of GluR-evoked responses in single cells and sho uld be instrumental in determining the factors capable of modifying ex citotoxicity.