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

Abstract:

: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.

journal_name

Brain Res

journal_title

Brain research

authors

Bender AS,Young LP,Norenberg MD

doi

10.1016/s0006-8993(96)01331-5

subject

Has Abstract

pub_date

1997-03-07 00:00:00

pages

59-66

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(96)01331-5

journal_volume

750

pub_type

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