Physiological release of excitatory amino acids.

The contribution of in vivo monitoring to the study of glutamate release is reviewed. Physiological stimulation increases both glutamate and aspartate in the extracellular compartment of the brain and both amino acids show Ca(2+)-dependent K(+)-evoked release. However, the finding that only glutamate is stored in synaptic vesicles implies that glutamate is the excitatory transmitter. Released glutamate is taken up into both neurones and glia by glutamate transporters. Uptake of glutamate, in addition to clearing the synapse, has a number of additional functions. Uptake into glia leads to the release of glutamine, which is involved in the recycling of transmitter glutamate; uptake into both neurones and glia leads to the release of ascorbate; uptake into glia leads to an increase glycolysis and export of lactate, an energy substrate for neuronal metabolism. Reversal of the glutamate transporter accounts for the parallel release of glutamate and aspartate from the cytoplasmic compartment. The basal concentration of extracellular glutamate is in the micromolar range. Such levels could lead to desensitisation of both NMDA and non-NMDA receptors. The functional implications of the level of basal glutamate are difficult to assess at present in view of the existence of multiple glutamate receptor subunits with different functional properties and distributions.