4.6 Article

Proton Fall or Bicarbonate Rise GLYCOLYTIC RATE IN MOUSE ASTROCYTES IS PAVED BY INTRACELLULAR ALKALINIZATION

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 291, Issue 36, Pages 19108-19117

Publisher

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M116.730143

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Funding

  1. Deutsche Forschungsgemeinschaft [DE 231/24-1,2]
  2. Priority Group of the Land Rheinland-Pfalz 'Bio-Comp' at the University of Kaiserslautern

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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.

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