Relationship between L-glutamate-regulated intracellular Na+ dynamics and ATP hydrolysis in astrocytes |
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Authors: | P J Magistretti J-Y Chatton |
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Institution: | (1) Department of Physiology, University of Lausanne and CHUV, Lausanne, Switzerland;(2) Center for Psychiatric Neurosciences, University of Lausanne and CHUV, Lausanne, Switzerland;(3) Cellular Imaging Facility, University of Lausanne and CHUV, Lausanne, Switzerland |
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Abstract: | Summary. 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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Keywords: | : Intracellular sodium energy metabolism fluorescence microscopy |
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