ATP steal between cation pumps: A mechanism linking Na+ influx to the onset of necrotic Ca2+ overload

J. Castro, I. Ruminot, O. H. Porras, C. M. Flores, T. Hermosilla, E. Verdugo, F. Venegas, S. Härtel, L. Michea, L. F. Barros*

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

20 Citas (Scopus)

Resumen

We set out to identify molecular mechanisms underlying the onset of necrotic Ca2+ overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca2+ chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca2+ was reduced by 60%, thus discarding a role for Ca2+ channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca2+ ATPase (PMCA). Remarkably, inhibition of the Na+/K+ ATPase rescued the PMCA and reverted the Ca2+ rise. Thermodynamic considerations suggest that the Ca2+ overload develops when the Na+/K+ ATPase, by virtue of the Na+ overload, clamps the ATP phosphorylation potential below the minimum required by the PMCA. In addition to providing the mechanism for the onset of Ca2+ overload, the crosstalk between cation pumps offers a novel explanation for the role of Na+ in cell death.

Idioma originalInglés
Páginas (desde-hasta)1675-1685
Número de páginas11
PublicaciónCell Death and Differentiation
Volumen13
N.º10
DOI
EstadoPublicada - 2006
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Biología molecular
  • Biología celular

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