ATP steal between cation pumps: A mechanism linking Na + influx to the onset of necrotic Ca 2+ overload

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

Keywords: proteins, permeability, inhibition, thermodynamics, membrane, transport, animals, phosphorylation, cells, ion, protein, cell, channel, stress, calcium, death, line, atpases, humans, human, gadolinium, sodium, dogs, atpase, epithelium, necrosis, mechanics, adenosine, molecular, article, cation, function, hela, controlled, register, animal, metabolic, oxidative, study, priority, chelation, nonhuman, journal, triphosphate, triphosphatase, biological, Models,, (potassium, sodium), Na(+)-K(+)-Exchanging, extracellular, (calcium), Calcium-Transporting


We set out to identify molecular mechanisms underlying the onset of necrotic Ca 2+ overload, triggered in two epithelial cell lines by oxidative stress or metabolic depletion. As reported earlier, the overload was inhibited by extracellular Ca 2+ chelation and the cation channel blocker gadolinium. However, the surface permeability to Ca 2+ was reduced by 60%, thus discarding a role for Ca 2+ channel/carrier activation. Instead, we registered a collapse of the plasma membrane Ca 2+ ATPase (PMCA). Remarkably, inhibition of the Na +/K + ATPase rescued the PMCA and reverted the Ca 2+ rise. Thermodynamic considerations suggest that the Ca 2+ 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 Ca 2+ 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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Volumen: 13
Número: 10
Editorial: Nature Publishing Group
Fecha de publicación: 2006
Página de inicio: 1675
Página final: 1685