Determinants of Deoxyglucose Uptake in Cultured Astrocytes: The Role of the Sodium Pump

Abstract

Glucose utilization in primary cell cultures of mouse cerebral astrocytes was studied by measuring uptake of tracer concentrations of [3H]-2-deoxyglucose ([3H]2-DG). The resting rate of glucose utilization, estimated at an extracellular K+ concentration ([K+]o) of 5.4 mM, was high (7.5 nmol glucose/mg protein/min), and it was similar in morphologically undifferentiated and differentiated (dibutyryl cAMP-pretreated) cultures. Resting uptake of [3H]2-DG was depressed by ouabain, by reducing [K+]o, and by cooling. Resting glucose utilization in astrocytes was dependent on Na pump activity. Na pump-dependent uptake in 2-3-wk-old cultures was .apprx. 50% of total [3H]2-DG uptake, but this fraction declined with culture age from 1-5 wk. Uptake was not affected by changes in extracellular bicarbonate concentration ([HCO3-]o) in the range of 5-50 mM, but it was significantly reduced in bicarbonate-free solution. At high [HCO3-]o (50 mM), uptake was insensitive to pH (pH 6-8), whereas at low [HCO3-]o (< 5 mM), uptake was markedly pH-dependent. Elevation of [K+]o from 2.3 mM to 14.2-20 mM (corresponding to extremes of the physiological range of [K+]o) resulted in a 35-43% increase in [3H]2-DG uptake that was not affected by culture age or by morphological differentiation. There is a high apparent rate of glucose utilization in astrocytes. This rate is dynamically responsive to changes in extracellular K+ concentration in the physiological range, and it is partially dependent on Na pump activity.