title: Differential dependence on Ca2+ of N-methyl-D-aspartate and quisqualate neurotoxicity in young rat hippocampal slices.
abstract: Exposure of slices of young (8 days old) rat hippocampus to 100 microM N-methyl-D-aspartate (NMDA) for 20 min followed by 90 min recovery, resulted in widespread, oedematous necrosis of all classes of neurones. The NMDA antagonist, D,L-2-amino-5-phosphonovalerate (APV) or omission of Ca2+ from the exposing solution prevented this cell death, but a large reduction in Cl- was ineffective. Quisqualate (100 microM, 20 min) led to a different pathological pattern characterised most strikingly by large numbers of cells undergoing 'dark cell degeneration'. Numerically, the neurones were affected in the order CA3 greater than CA1 greater than dentate granule cells. Quisqualate toxicity was not prevented by APV nor by reducing Ca2+ or Cl-. It is concluded that, as in cerebellar slices (but unlike in cultures of hippocampal neurones) NMDA toxicity in hippocampal slices is Ca2+-dependent and Cl- -independent. However, quisqualate exerts its pathological effects through a different mechanism. This mechanism may be primarily metabolic rather than ionic.
authors: Department of Physiology, University of Liverpool, U.K.
authors: G
authors: G
authors: Garthwaite
authors: J
authors: J
authors: Garthwaite
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D002712:Chlorides / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000633:toxicity*; D016318:Quisqualic Acid; D051381:Rats; D013194:Staining and Labeling
chemical_list: D002712:Chlorides; D010069:Oxadiazoles; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002118:Calcium