title: Acute feedback control of astrocytic glycolysis by lactate.
abstract: Neuronal activity is accompanied by a rapid increase in interstitial lactate, which is hypothesized to serve as a fuel for neurons and a signal for local vasodilation. Using FRET microscopy, we report here that the rate of glycolysis in cultured mice astrocytes can be acutely modulated by physiological changes in extracellular lactate. Glycolytic inhibition by lactate was not accompanied by detectable variations in intracellular pH or intracellular ATP and was not dependent of mitochondrial function. Pyruvate was also inhibitory, suggesting that the effect of lactate is not mediated by the NADH/NAD(+) ratio. We propose that lactate serves as a fast negative feedback signal limiting its own production by astrocytes and therefore the amplitude of the lactate surge. The inhibition of glucose usage by lactate was much stronger in resting astrocytes than in K(+)-stimulated astrocytes, which suggests that lactate may also help diverting glucose from resting to active zones.
authors.affiliation: Centro de Estudios Científicos (CECs), Av. Arturo Prat 514, Casilla 1469, Valdivia, Chile.
authors.forename: T
authors.initials: T
authors.lastname: Sotelo-Hitschfeld
authors.forename: I
authors.initials: I
authors.lastname: Fernández-Moncada
authors.forename: L F
authors.initials: LF
authors.lastname: Barros
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003571:Cytochalasin B / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D019807:Iodoacetic Acid / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011188:Potassium / Q000494:pharmacology; D061209:Proton Ionophores / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D061209:Proton Ionophores; D012402:Rotenone; D019344:Lactic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D003571:Cytochalasin B; D000255:Adenosine Triphosphate; D005947:Glucose; D011188:Potassium; D019807:Iodoacetic Acid