The Contribution of GABA to Glutamate/Glutamine Cycling and Energy Metabolism in the Rat Cortex in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 102; no. 15; pp. 5588 - 5593
• Main Authors: Patel, Anant B., de Graaf, Robin A., Mason, Graeme F., Rothman, Douglas L., Shulman, Robert G., Behar, Kevin L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 12.04.2005; National Acad Sciences
• Subjects: Acetates; Acetates - administration & dosage; Acetates - blood; Acetates - metabolism; Acetates - pharmacology; Amino acids; Amino Acids - metabolism; Anesthesia; Anesthetics, Inhalation - pharmacology; Animals; Biological Sciences; Biological Transport - drug effects; Blood Glucose - analysis; Brain; Brain research; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Energy metabolism; Energy Metabolism - drug effects; Energy Metabolism - physiology; GABA Modulators - pharmacology; gamma-Aminobutyric Acid - biosynthesis; gamma-Aminobutyric Acid - metabolism; Glucose - administration & dosage; Glucose - pharmacology; Glutamic Acid - metabolism; Glutamine - metabolism; Halothane - pharmacology; Magnetic Resonance Spectroscopy; Male; Metabolism; Neuroglia; Neuroglia - drug effects; Neuroglia - metabolism; Neurology; Neurons; Neurons - drug effects; Neurons - metabolism; Neurotransmitters; Oxidation; Oxidation-Reduction; Pentobarbital - pharmacology; Rats; Rats, Sprague-Dawley; Rodents; Synapses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0501703102

Previous studies have shown that the glutamate/glutamine (Glu/Gln) neurotransmitter cycle and neuronal glucose oxidation are proportional (1:1), with increasing neuronal activity above isoelectricity. GABA, a product of Glu metabolism, is synthesized from astroglial Gln and contributes to total Glu/Gln neurotransmitter cycling, although the fraction contributed by GABA is unknown. In the present study, we used13C NMR spectroscopy together with i.v. infusions of [1,6-13C2]glucose and [2-13C]acetate to separately determine rates of Glu/Gln and GABA/Gln cycling and their respective tricarboxylic acid cycles in the rat cortex under conditions of halothane anesthesia and pentobarbital-induced isoelectricity. Under 1% halothane anesthesia, GABA/Gln cycle flux comprised 23% of total (Glu plus GABA) neurotransmitter cycling and 18% of total neuronal tricarboxylic acid cycle flux. In isoelectric cortex, glucose oxidation was reduced >3-fold in glutamatergic and GABAergic neurons, and neurotransmitter cycling was below detection. Hence, in both cell types, the primary energetic costs are associated with neurotransmission, which increase together as cortical activity is increased. The contribution of GABAergic neurons and inhibition to cortical energy metabolism has broad implications for the interpretation of functional imaging signals.