Relationship between L-glutamate-regulated intracellular Na+ dynamics and ATP hydrolysis in astrocytes

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Abstract
Glutamate uptake into astrocytes and the resulting increase in intracellular Na+ (Na+ i) have been identified as a key signal coupling excitatory neuronal activity to increased glucose utilization. Arguments based mostly on mathematical modeling led to the conclusion that physiological concentrations of glutamate more than double astrocytic Na+/K+-ATPase activity, which should proportionally increase its ATP hydrolysis rate. This hypothesis was tested in the present study by fluorescence monitoring of free Mg2+ (Mg2+ i), a parameter that inversely correlates with ATP levels. Glutamate application measurably increased Mg2+ i (i.e. decreased ATP), which was reversible after glutamate washout. Na+ i and ATP changes were then directly compared by simultaneous Na+ i and Mg2+ imaging. Glutamate increased both parameters with different rates and blocking the Na+/K+-ATPase during the glutamate-evoked Na+ i response, resulted in a drop of Mg2+ i levels (i.e. increased ATP). Taken together, this study demonstrates the tight correlation between glutamate transport, Na+ homeostasis and ATP levels in astrocytes.

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