title: Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing.
abstract: Neural activity has been suggested to initially trigger ATP production by glycolysis, rather than oxidative phosphorylation, for three reasons: glycolytic enzymes are associated with ion pumps; neurons may increase their energy supply by activating glycolysis in astrocytes to generate lactate; and activity increases glucose uptake more than O₂ uptake. In rat hippocampal slices, neuronal activity rapidly decreased the levels of extracellular O₂ and intracellular NADH (reduced nicotinamide adenine dinucleotide), even with lactate dehydrogenase blocked to prevent lactate generation, or with only 20% superfused O₂ to mimic physiological O₂ levels. Pharmacological analysis revealed an energy budget in which 11% of O₂ use was on presynaptic action potentials, 17% was on presynaptic Ca²⁺ entry and transmitter release, 46% was on postsynaptic glutamate receptors, and 26% was on postsynaptic action potentials, in approximate accord with theoretical brain energy budgets. Thus, the major mechanisms mediating brain information processing are all initially powered by oxidative phosphorylation, and an astrocyte-neuron lactate shuttle is not needed for this to occur.
authors: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors: Catherine N
authors: CN
authors: Hall
authors: Miriam C
authors: MC
authors: Klein-Flügge
authors: Clare
authors: C
authors: Howarth
authors: David
authors: D
authors: Attwell
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019256:Cadmium Chloride / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006019:Glycolysis / Q000502:physiology; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009930:Organic Chemicals / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009930:Organic Chemicals; D026941:Sodium Channel Blockers; D009243:NAD; D019344:Lactic Acid; D013779:Tetrodotoxin; C048603:oxamate (repellent); D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D000255:Adenosine Triphosphate; D014633:Valine; D019256:Cadmium Chloride; D010100:Oxygen