Chatton JY Pellerin L Magistretti PJ 2003 Synaptically released glutamate has been identified as a signal coupling excitatory neuronal activity to increased glucose utilization. The proposed mechanism of this coupling involves glutamate uptake into astrocytes resulting in increased intracellular Na+ (Nai+) and activation of the Na+/K+-ATPase. Increased metabolic demand linked to disruption of Nai+ homeostasis activates glucose uptake and glycolysis in astrocytes. Here, we have examined whether a similar neurometabolic coupling could operate for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), also taken up by Na+-dependent transporters into astrocytes. Thus, we have compared the Nai+ response to GABA and glutamate in mouse astrocytes by microspectrofluorimetry. The Nai+ response to GABA consisted of a rapid rise of 4-6 mM followed by a plateau that did not, however, significantly activate the pump. Indeed, the GABA transporter-evoked Na+ influxes are transient in nature, almost totally shutting off within approximately 30 sec of GABA application. The metabolic consequences of the GABA-induced Nai+ response were evaluated by monitoring cellular ATP changes indirectly in single cells and measuring 2-deoxyglucose uptake in astrocyte populations. Both approaches showed that, whereas glutamate induced a robust metabolic response in astrocytes (decreased ATP levels and glucose uptake stimulation), GABA did not cause any measurable metabolic response, consistent with the Nai+ measurements. Results indicate that GABA does not couple inhibitory neuronal activity with glucose utilization, as does glutamate for excitatory neurotransmission, and suggest that GABA-mediated synaptic transmission does not contribute directly to brain imaging signals based on deoxyglucose. application/pdf https://sonar.ch/global/documents/189525 eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2132096100 info:eu-repo/semantics/altIdentifier/pmid/14530410 info:eu-repo/semantics/openAccess Proceedings of the National Academy of Sciences of the United States of America. - 2003 Animals Astrocytes Biological Transport, Active Brain Cells, Cultured Deoxyglucose Glutamic Acid Intracellular Fluid Lactic Acid Magnesium Mice Nipecotic Acids Pyridines Sodium Sodium-Potassium-Exchanging ATPase Synaptic Transmission gamma-Aminobutyric Acid GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission. http://purl.org/coar/resource_type/c_6501