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

Ignacio Fernández-Moncada, L. Felipe Barros*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

35 Citas (Scopus)

Resumen

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. In the present study, 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+ pumpwas assessed in parallelwith the Na+ -sensitive dye SBFI AM (Na+ -binding benzofuran isophthalate acetoxymethyl ester). OXPHOS (oxidative phosphorylation) inhibition resulted in bulk ATP depletion and a 5-fold stimulation of glycolytic flux, in spite of which Na+ pumping was inhibited by 90%. Mathematical modelling 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 is not energetic and that the pump is mainly fuelled by mitochondrial ATP.

Idioma originalInglés
Páginas (desde-hasta)353-361
Número de páginas9
PublicaciónBiochemical Journal
Volumen460
N.º3
DOI
EstadoPublicada - 2014
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología molecular
  • Biología celular

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