Increase in the stimulation-induced overflow of excitatory amino acids from hippocampal slices: interaction between low glucose concentration and fluoroacetate.

To see whether the enhanced evoked release of aspartate and glutamate in the presence of low glucose concentration is due to a decreased glial uptake, the electrical-field stimulation induced release of aspartate and glutamate was measured in rat hippocampal slices in the presence of 5 or 0.2 mM glucose and of graded concentrations of fluoroacetate, a specific inhibitor of glial tricarboxylic acid cycle. In 5 mM glucose, fluoroacetate increased the overflow of both excitatory amino acids equally in a dose-dependent manner, with a maximal effect obtained at 2 mM. This maximal increase of glutamate overflow was about the same as caused by 0.2 mM glucose, but low glucose increased aspartate overflow 5 times more than did fluoroacetate. Fluoroacetate failed to increase any further the large evoked overflow of either glutamate or aspartate induced by 0.2 mM glucose. The absence of an additive effect of fluoroacetate and of low glucose suggests that under both conditions the increased overflow of glutamate is due to a reduced glial uptake. In low glucose an increased synthesis also contributes to the additional large release of aspartate.