Relationship between L-glutamate-regulated intracellular Na+ dynamics and ATP hydrolysis in astrocytes.
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.
Magistretti
P J
PJ
Department of Physiology, University of Lausanne and CHUV, Lausanne, Switzerland.
Chatton
J-Y
JY
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D006868:Hydrolysis / Q000187:drug effects; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D012964:Sodium / Q000502:physiology*
D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D012964:Sodium