Neurotoxicity of excitatory amino acid receptor agonists in rat cerebellar slices: dependence on calcium concentration.

In slices of developing rat cerebellum, a 30-min application of the excitatory amino acid receptor agonist, N-methyl-D-aspartate (NMDA), led to the necrosis of differentiating granule cells and deep nuclear neurones. The corresponding effect of another agonist, kainate, was the death of Golgi cells. The toxic effects of both agonists were prevented if the concentration of calcium in the exposing solution was reduced to 0.3 mM from the control level of 2.5 mM. A lesser reduction (to 1 mM) was enough to prevent 90% of the NMDA-induced necrosis of granule cells. The results indicate that an important component of the acute neurotoxic effects of excitatory amino acids is calcium-dependent and suggest reasons why this may not have been revealed in some previous studies.