Glutamate Uptake Stimulates Na+,K+-ATPase Activity in Astrocytes via Activation of a Distinct Subunit Highly Sensitive to Ouabain |
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Authors: | Luc Pellerin Pierre J. Magistretti |
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Affiliation: | Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Facultéde Médecine, Universitéde Lausanne, Lausanne, Switzerland |
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Abstract: | 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 µ M . 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 ( K 0.5 = 113 µ M ), 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 ( K 0.5 = 20 n M ), 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. |
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Keywords: | Sodium pump Glutamate transporter Energy metabolism Glia |
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