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 original | Inglés |
---|---|
Páginas (desde-hasta) | 1675-1685 |
Número de páginas | 11 |
Publicación | Cell Death and Differentiation |
Volumen | 13 |
N.º | 10 |
DOI | |
Estado | Publicada - 2006 |
Publicado de forma externa | Sí |
Áreas temáticas de ASJC Scopus
- Biología molecular
- Biología celular