Continuous glutamate leakage from brain cells is balanced by compensatory high-affinity reuptake transport.

The glutamate (and aspartate) uptake blocker threo-3-hydroxyaspartate (20 microM) was added to superfusion fluids employed for in vivo microdialysis of corpus striatum, and to incubation medium for striatal slices (5 microM). In vivo it caused an increase in glutamate and aspartate concentrations in the superfusion fluid. In vitro it caused increases in the levels of glutamate, aspartate, GABA, taurine and glutamine in the incubation fluid. Tetrodotoxin (1 microM) did not influence the rises in glutamate or aspartate. It is concluded from these results that there is a continuous outward leakage of glutamate, and aspartate, from neural cells which is normally balanced by an inward flux due to reuptake processes. This leakage is distinct from synaptic release of these substances due to spike activity, since tetrodotoxin added to striatal slices did not diminish the action of threo-3-hydroxyaspartate. The significance of the findings for mechanisms leading to ischaemic or hypoxic brain damage, and basic mechanisms in epilepsy is discussed.