GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission.
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.
Chatton
Jean-Yves
JY
Institute of Physiology, Centre Hospitalier Universitaire Vaudois, University of Lausanne Medical School, 1005 Lausanne, Switzerland. jean-yves.chatton@iphysiol.unil.ch
Pellerin
Luc
L
Magistretti
Pierre J
PJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D009557:Nipecotic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D009557:Nipecotic Acids; D011725:Pyridines; D019344:Lactic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D003847:Deoxyglucose; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; C067012:CI 966