Non-preferential fuelling of the Na{+}/K{+} ATPase pump

There is abundant evidence that glycolysis and the Na+/K+ ATPase pump are functionally coupled, and it is thought that the nature of the coupling is energetic, with glycolysis providing the ATP that fuels the pump. This notion has been instrumental to current models of brain energy metabolism. However structural and biophysical considerations suggest that the pump should also have access to mitochondrial ATP, which is much more abundant. Here we have investigated the source of ATP that fuels the Na+ pump in astrocytes, taking advantage of the high temporal resolution of recently-available FRET nanosensors for glucose, lactate and ATP. The activity of the Na+ pump was assessed in parallel with the Na+-sensitive dye SBFI. OXPHOS inhibition resulted in bulk ATP depletion and a 5-fold stimulation of glycolytic flux, despite of which Na+ pumping was inhibited by 90%. Mathematical modeling of ATP dynamics showed that the observed pump failure is inconsistent with preferential fuelling of the Na+ pump by glycolytic ATP. We conclude that the nature of the functional coupling between the Na+ pump and the glycolytic machinery in not energetic and that the pump is mainly fuelled by mitochondrial ATP.
Source: BJ Energy - Category: Biochemistry Authors: Tags: BJ Energy Source Type: research