Js. Isaacson et Ra. Nicoll, THE UPTAKE INHIBITOR L-TRANS-PDC ENHANCES RESPONSES TO GLUTAMATE BUT FAILS TO ALTER THE KINETICS OF EXCITATORY SYNAPTIC CURRENTS IN THE HIPPOCAMPUS, Journal of neurophysiology, 70(5), 1993, pp. 2187-2191
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.