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GABA uptake into astrocytes is not associated with significant metabolic cost: Implications for brain imaging of inhibitory transmission

2003; National Academy of Sciences; Volume: 100; Issue: 21 Linguagem: Inglês

10.1073/pnas.2132096100

1091-6490

Jean‐Yves Chatton, Luc Pellerin, Pierre J. Magistretti,

Neuroinflammation and Neurodegeneration Mechanisms

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 + (Na i + ) and activation of the Na + /K + -ATPase. Increased metabolic demand linked to disruption of Na i + homeostasis activates glucose uptake and glycolysis in astrocytes. Here, we have examined whether a similar neurometabolic coupling could operate for the inhibitory neurotransmitter γ-aminobutyric acid (GABA), also taken up by Na + -dependent transporters into astrocytes. Thus, we have compared the Na i + response to GABA and glutamate in mouse astrocytes by microspectrofluorimetry. The Na i + 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 ≈30 sec of GABA application. The metabolic consequences of the GABA-induced Na i + 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 Na i + 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.