We have studied the effects of blockers of glutamate transporters on e
xcitatory synaptic transmission to determine whether transporters incr
ease the clearance rate of transmitter from the synaptic cleft on the
millisecond time scale. The transporter blockers Li+ and THA increased
the amplitude, but not the decay time, of spontaneous miniature AMPA
receptor EPSCs recorded at 34 degrees C but not 24 degrees C. Evoked A
MPA receptor EPSCs were similarly affected by THA. The rapidly dissoci
ating AMPA receptor competitive antagonist PDA inhibited evoked AMPA r
eceptor EPSCs less in the presence of THA at both temperatures, implyi
ng that transporter blockade slows clearance. We suggest that transpor
ters speed glutamate clearance mainly by binding glutamate and that AM
PA receptors are not saturated by synaptically released glutamate at 3
4 degrees C.