Effect of lactic acid on L-glutamate uptake in cultured astrocytes: mechanistic considerations.
Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit L-glutamate (L-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit L-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of L-Glu uptake by 65%. HCl (pH 6.1) also inhibited L-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on L-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling 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-Glu 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-Glu uptake by lactic acid in astrocytes.
Bender
A S
AS
Veterans Administration Medical Center, Department of Pathology, University of Miami School of Medicine, FL, USA.
Young
L P
LP
Norenberg
M D
MD
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019344:Lactic Acid / Q000494:pharmacology*; D051381:Rats; D013696:Temperature
D019344:Lactic Acid; D018698:Glutamic Acid; D006851:Hydrochloric Acid