title: Proton Fall or Bicarbonate Rise: GLYCOLYTIC RATE IN MOUSE ASTROCYTES IS PAVED BY INTRACELLULAR ALKALINIZATION.
abstract: Glycolysis is the primary step for major energy production in the cell. There is strong evidence suggesting that glucose consumption and rate of glycolysis are highly modulated by cytosolic pH/[H(+)], but those can also be stimulated by an increase in the intracellular [HCO3 (-)]. Because proton and bicarbonate shift concomitantly, it remained unclear whether enhanced glucose consumption and glycolytic rate were mediated by the changes in intracellular [H(+)] or [HCO3 (-)]. We have asked whether glucose metabolism is enhanced by either a fall in intracellular [H(+)] or a rise in intracellular [HCO3 (-)], or by both, in mammalian astrocytes. We have recorded intracellular glucose in mouse astrocytes using a FRET-based nanosensor, while imposing different intracellular [H(+)] and [CO2]/[HCO3 (-)]. Glucose consumption and glycolytic rate were augmented by a fall in intracellular [H(+)], irrespective of a concomitant rise or fall in intracellular [HCO3 (-)]. Transport of HCO3 (-) into and out of astrocytes by the electrogenic sodium bicarbonate cotransporter (NBCe1) played a crucial role in causing changes in intracellular pH and [HCO3 (-)], but was not obligatory for the pH-dependent changes in glucose metabolism. Our results clearly show that it is the cytosolic pH that modulates glucose metabolism in cortical astrocytes, and possibly also in other cell types.
authors.affiliation: From the Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserlautern, P. B. 3049, D-67653 Kaiserslautern, Germany and theparambil@biologie.uni-kl.de.
authors.forename: Shefeeq M
authors.initials: SM
authors.lastname: Theparambil
authors.affiliation: From the Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserlautern, P. B. 3049, D-67653 Kaiserslautern, Germany and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weber
authors.affiliation: From the Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserlautern, P. B. 3049, D-67653 Kaiserslautern, Germany and.
authors.forename: Jana
authors.initials: J
authors.lastname: Schmälzle
authors.affiliation: From the Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserlautern, P. B. 3049, D-67653 Kaiserslautern, Germany and the Centro de Estudios Científicos (CECs), Valdivia 5110466, Chile.
authors.forename: Ivàn
authors.initials: I
authors.lastname: Ruminot
authors.affiliation: From the Abteilung für Allgemeine Zoologie, FB Biologie, University of Kaiserlautern, P. B. 3049, D-67653 Kaiserslautern, Germany and deitmer@biologie.uni-kl.de.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018345:Mice, Knockout; D011522:Protons; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D011522:Protons; D027982:Sodium-Bicarbonate Symporters; D005947:Glucose
keywords: FRET nanosensor; FRET nanosensors; astrocyte; astrocytes; bicarbonate; brain metabolism; glucose; metabolism; pH