Glutamate uptake stimulates Na+, K+-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain

Luc Pellerin*, Pierre J. Magistretti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

The excitatory amino acid glutamate was previously shown to stimulate aerobic glycolysis in astrocytes by a mechanism involving its uptake through an Na+-dependent transporter. Evidence had been provided that Na+,K+- ATPase might be involved in this process. We have now measured the activity of Na+,K+-ATPase in cultured astrocytes, using ouabain-sensitive 86Rb uptake as an index. L-Glutamate increases glial Na+,K+ATPase activity in a concentration-dependent manner with an EC50 = 67 μM. Both L- and D- aspartate, but not D-glutamate, produce a similar response, an observation that is consistent with an uptake-related effect rather than a receptor- mediated one. Under basal conditions, concentration-dependent inhibition of Na+,K+-ATPase activity in astrocytes by ouabain indicates the presence of a single catalytic site with a low affinity for ouabain (K0.5 = 1.13 μM), compatible with the presence of an α1 isozyme. On stimulation with glutamate, however, most of the increased activity is inhibited by low concentrations of ouabain (K0.5 = 20 nM), thus revealing a high-affinity site akin to the α2 isozyme. These results suggest that astrocytes possess a glutamate-sensitive isoform of Na+,K+-ATPase that can be mobilized in response to increased neuronal activity.

Original languageEnglish (US)
Pages (from-to)2132-2137
Number of pages6
JournalJournal of Neurochemistry
Volume69
Issue number5
DOIs
StatePublished - Nov 1997
Externally publishedYes

Keywords

  • Energy metabolism
  • Glia
  • Glutamate transporter
  • Sodium pump

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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