The effect of glutamate uptake inhibitors on hippocampal evoked potentials in vitro.

The influence of four inhibitors of the high-affinity glutamate uptake system (DL-aspartic acid P-hydroxymate, DL-AHM; L-aspartic acid P-hydroxymate, L-AHM; threo-P-methylaspartate, DLM; L-transpyrrolidine-2,4-dicarboxylate, PDC) on potentials recorded from hippocampal slices was investigated. At low concentrations of DL-AHM, L-AHM and DLM (50 150 yM) the population spike was permanently amplified. NMDA receptor antagonists blocked this facilitatory effect of L-AHM, DL-AHM and DLM. At higher concentrations (400-700 yM) DL-AHM and DLM abolished the population spike, while L-AHM did not eliminate the population spike at any concentration tested. None of these uptake inhibitors influenced an antidromic potential recorded in ca2+ -free Ringer solution. PDC at lower concentrations (75 yM) did not affect the population spike and at higher concentrations (150 yM 500 pM) induced only a transient elevation in population spike. Our data demonstrate that modification of glutamate uptake may be an important factor in the regulation of synaptic efficiency of glutamergic pathways. 'TO whom correspondence should be addressed