ATP depletion caused by menadione and triethyllead in isolated hepatocytes is associated with intracellular acidosis and a sustained increase in intracellular Na+ and Ca2+ concentrations. Removal of Na+ from the incubation medium as well as the inclusion of EGTA largely prevented the increase in cytosolic Ca2+, thus indicating that Ca2+ was mobilized from the extracellular medium in response to Na+ load. To further validate these findings, hepatocytes were incubated with a combination of sodium propionate and ouabain in order to induce intracellular acidosis and inhibit Na+ extrusion. This treatment promoted a marked increase in intracellular Na+ and Ca2+ concentrations that was prevented by omission of Na+ from the incubation medium as well as by agents that inhibited cellular Na+ influx. These data indicate that following Na+ load, Ca2+ can be accumulated in hepatocytes via a Na+/Ca2+ antiporter operating on a reverse mode.
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