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

Castro J.; Ruminot, I; Porras, OH; Flores, CM; Hermosilla T.; Verdugo E.; Venegas, F; Hartel, S; Michea, L.; Barros, LF

Abstract

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. © 2006 Nature Publishing Group. All rights reserved.

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Título según WOS: ATP steal between cation pumps: a mechanism linking Na+ influx to the onset of necrotic Ca2+ overload
Título según SCOPUS: ATP steal between cation pumps: A mechanism linking Na+ influx to the onset of necrotic Ca2+ overload
Título de la Revista: CELL DEATH AND DIFFERENTIATION
Volumen: 13
Número: 10
Editorial: Nature Publishing Group
Fecha de publicación: 2006
Página de inicio: 1675
Página final: 1685
Idioma: English
URL: http://www.nature.com/doifinder/10.1038/sj.cdd.4401852
DOI:

10.1038/sj.cdd.4401852

Notas: ISI, SCOPUS