GLUTAMATE‐INDUCED CALCIUM LOADS: EFFECTS ON ENERGY METABOLISM AND NEURONAL VIABILITY

1. Glutamate‐induced increases in intracellular free Ca²⁺ concentration ([Ca²⁺]i) were recorded from cultured rat hippocampal neurons with single cell microfluorometry. The [Ca²⁺]i increase did not correlate with glutamate‐induced cell death, consistent with the idea that Ca²⁺ accumulates in an intracellular store, and that loading this store might be toxic. 2. Glutamate‐induced Ca²⁺ loads were buffered by a low‐affinity, high‐capacity process that was inhibited by the mitochondrial uncoupling agent FCCP and modulated by intracellular Na⁺. 3. Glutamate‐induced Ca²⁺ loads also produced an intracellular acidification. The acidification was prevented by the metabolic inhibitor 2‐deoxyglucose, mimicked by Ba²⁺, and inhibited by microinjection of ruthenium red. 4. These data are consistent with the hypothesis that mitochondria sequester glutamate‐induced Ca²⁺ loads producing a metabolic acidosis; metabolic stress may contribute to glutamate‐induced neuronal death.