Glutamate-induced energetic stress in hippocampal slices: evidence against NMDA and glutamate uptake as mediators

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.