Effect of lactic acid on L-glutamate uptake in cultured astrocytes: Mechanistic considerations

Alex S. Bender, Laurence P. Young, Michael D. Norenberg

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalBrain research
Issue number1-2
StatePublished - Mar 7 1997


  • astrocyte
  • cell swelling
  • glutamate release
  • glutamate uptake
  • hypothermia
  • lactic acid
  • potassium ion release

ASJC Scopus subject areas

  • Neuroscience(all)


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