ASTROCYTE GLUCOSE-METABOLISM UNDER NORMAL AND PATHOLOGICAL CONDITIONSIN-VITRO

Astrocytes in primary culture produce lactate. The net production of l actate from glucose requires that the carbon flux through glycolysis e xceed the carbon flux to CO2. This study investigates the control and function of this 'excess' glycolysis in astrocyte cultures. Blockade o f glycolysis was found to have minimal effects on astrocyte ATP and fu nction if other substrates for oxidative metabolism were available. In contrast, selective blockade of oxidative metabolism reduced adenosin e triphosphate (ATP) levels and slowed glutamate uptake despite a mark ed increase in glycolytic rate. Acidosis suppressed both glucose utili zation and lactate production but had minimal effects on ATP levels, A cidosis in combination with blockade of oxidative metabolism blunted t he increase in glycolytic rate and accentuated ATP depletion relative to oxidative blockade alone. These studies suggest that glycolysis in astrocyte cultures is regulated by factors other than energy demand, a nd that the capacity of glycolysis to support astrocyte metabolism dur ing hypoxia is markedly pH dependent.