EFFECT OF LACTIC-ACID ON L-GLUTAMATE UPTAKE IN CULTURED ASTROCYTES - MECHANISTIC CONSIDERATIONS

Elevated levels of lactic acid can be deleterious to CNS tissue. Lacti c acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit L-glutamate (L-Glu) uptake, we examined whet her one of the actions of lactic acid is to inhibit L-Glu uptake. Astr ocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhi bition of L-Glu uptake by 65%. HCl (pH 6.1) also inhibited L-Glu uptak e and this inhibition was potentiated by sodium lactate (25 mM). The i nhibitory effect of lactic acid on L-Glu uptake was partially reversib le and the reversibility was enhanced by hypothermia. Blocking glial s welling with D-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on L-Glu uptake, indicating that swelling per se or free radicals, were not the factors in L-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of L-Gl u release and a seven-fold increase of K+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K+ and L-Glu release which may be a factor in the inhibition of L-G lu uptake by lactic acid in astrocytes.