THE UPTAKE INHIBITOR L-TRANS-PDC ENHANCES RESPONSES TO GLUTAMATE BUT FAILS TO ALTER THE KINETICS OF EXCITATORY SYNAPTIC CURRENTS IN THE HIPPOCAMPUS

1. We have used patch-clamp recording techniques to study the physiolo gical properties of a recently described glutamate uptake blocker, L-t rans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), in the CA1 regio n of the guinea pig hippocampus. 2. L-trans-PDC markedly potentiated t he action of exogenously applied glutamate and raised the ambient extr acellular levels of glutamate in hippocampal slices. Despite these act ions, L-trans-PDC did not affect the time course of either the N-methy l-D-aspartate (NMDA) or non-NMDA receptor-mediated synaptic currents e voked by the stimulation of a large number of neighboring synapses. 3. These findings are consistent with models of fast synaptic transmissi on in which transmitter is rapidly cleared from the synaptic cleft by diffusion. However, in marked contrast to fast gamma-aminobutyric acid A (GABA(A)) synapses in the hippocampus, uptake does not appear to pl ay a role in regulating the ''spill-over' of transmitter from neighbor ing, co-activated glutamatergic synapses. Therefore, either diffusion alone can effectively limit the temporal and spatial domain of synapti cally released glutamate, or alternatively, L-trans-PDC like other cur rently available blockers is not sufficiently potent to reveal a role for transmitter uptake at glutamatergic synapses.