Abstract
The introduction of exogenous glutamate to normally respiring hippocampal slices produced substantial reductions in ATP, phosphocreatine (PCr) and intracellular pH (pHi) when the concentration exceeded 1 mM. These changes were not prevented by addition of MK-801 (an NMDA receptor antagonist), nor were they mimicked by NMDA or high potassium. In addition, the glutamate-induced metabolic alterations were not prevented by addition of aspartate-b-hydroxymate or sodium substitution by choline, both of which should inhibit high-affinity sodium-dependent glutamate uptake. These results suggest that glutamate alone can produce marked energetic stress in neural tissue, even when glucose and oxygen are maintained at control levels; and that the energetic stress does not appear to be specifically mediated by NMDA-induced depolarization, or by high-affinity uptake of glutamate.
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Whittingham, T.S., Assaf, H., Selman, W.R. et al. Glutamate-induced energetic stress in hippocampal slices: Evidence against NMDA and glutamate uptake as mediators. Metabolic Brain Disease 7, 77–92 (1992). https://doi.org/10.1007/BF01000147
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DOI: https://doi.org/10.1007/BF01000147