Glutamate neurotoxicity in cortical cell culture is calcium dependent

Brief exposure to glutamate produced widespread neuronal death in mature, but not young, cortical cell cultures. Extracellular sodium replacement or addition of tetrodotoxin produced only minor reduction in this toxic neuronal loss. However, removal of extracellular calcium markedly reduced neuronal loss, and elevation of extracellular calcium accentuated neuronal loss. These observations suggest that the toxicity of glutamate on cortical neurons may depend primarily on the presence of extracellular Ca, probably through a mechanism which is distinct from simple 'excitotoxicity'.