Amino acid neurotoxicity: intracellular sites of calcium accumulation associated with the onset of irreversible damage to rat cerebellar neurones in vitro.

Electron microscopy and the combined oxalate-pyroantimonate technique were used to locate calcium in intracerebellar nucleus neurones of rat cerebellar slices subjected to a neurotoxic concentration of N-methyl-D-aspartate. After a sub-lethal exposure period (5 min) calcium pyroantimonate deposits were found in swollen cisterns of the Golgi apparatus and, in lesser amounts, in the nuclei. Deposits were more prominent in the nuclei after a just-lethal exposure (10 min) when they were additionally observed within a population of swollen mitochondria and also apparently free in the dendritic and somatic cytoplasm. The results support the proposal that amino acid neurotoxicity is a consequence of an intracellular Ca2+ overload brought about by excessive Ca2+ influx.