Block of glutamate transporters potentiates postsynaptic excitation

We have studied the effects of blockers of glutamate transporters on excitatory synaptic transmission to determine whether transporters increase 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°C but not 24°C. Evoked AMPA receptor EPSCs were similarly affected by THA. The rapidly dissociating AMPA receptor competitive antagonist PDA inhibited evoked AMPA receptor EPSCs less in the presence of THA at both temperatures, implying that transporter blockade slows clearance. We suggest that transporters speed glutamate clearance mainly by binding glutamate and that AMPA receptors are not saturated by synaptically released glutamate at 34°C.