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 beta-hydroxymate, DL-AHM; L-aspartic acid beta-hydroxymate, L-AHM; threo-beta-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 microM) 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 microM) 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 Ca(2+)- free Ringer solution. PDC at lower concentrations (75 microM) did not affect the population spike and at higher concentrations (150 microM-500 microM) 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.
El-Sherif
Y
Y
CSI/IBR Center for Developmental Neuroscience, College of Staten Island/CUNY 10314, USA.
Singh
N
N
Khan
T
T
Wieraszko
A
A
D000818:Animals; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects* / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*
D003998:Dicarboxylic Acids; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; C024848:beta-aspartylhydroxamic acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D001216:Asparagine; C083486:pyrrolidine-2,4-dicarboxylic acid