Active role of glutamate uptake in the synaptic transmission from retinal nonspiking neurons

We examined the role of glutamate uptake in the synaptic transmission of gr aded responses from newt retinal bipolar cells (BCs) to ganglion layer cell s (GLCs). In dissociated Muller cells (retinal glia), glutamate evoked an u ptake current that was effectively inhibited by L-trans-pyrrolidine-2,4-dic arboxylic acid (PDC). PDC had no effect on the non-NMDA receptors of dissoc iated spiking neurons. In the retinal slice preparation, dual whole-cell re cordings were performed from a pair of BC and GLC. A depolarizing pulse app lied to a BC activated the Ca2+ current (I-Ca) in the BC and evoked an EPSC in the GLC. Application of PDC prolonged both non-NMDA and NMDA receptor-m ediated components of the evoked EPSC but changed neither the amplitude nor time course of I-Ca. When the slice preparation was superfused with a solu tion containing glutamate but not PDC, the evoked EPSC decreased in amplitu de without changing the time course, suggesting that the prolongation of th e evoked EPSC is not attributable to a simple increase in ambient glutamate concentration after inhibition of glutamate uptake. Because PDC did not af fect the amplitude, time course, or frequency of spontaneous EPSCs, it is u nlikely that PDC modified presynaptic and/or postsynaptic mechanisms. These results indicate that inhibition of glutamate uptake slows the clearance o f glutamate accumulated in the synaptic cleft by multiple quantal release a nd prolongs the evoked EPSC. The role of glutamate uptake at synapses in th e inner retina is not only to maintain the extracellular glutamate concentr ation at a low level but also to terminate the light-evoked EPSCs rapidly.