Mg2+ mitigates Ca2+-dependent cell killing by ionophore A23187.

The Ca2+, Mg2+ ionophore A23187 kills cultured cells in a manner which is dependent upon millimolar concentrations of Ca2+ (Schanne et al., 1979). The killing is thought to be caused by an increase in the cellular Ca2+ content following exposure of cells to the ionophore. We have found that the Ca2+-dependent killing of Balb/c 3T3 cells by ionophore A23187 is reversed by raising, and potentiated by lowering, the extracellular Mg2+ concentration. Ionophore treatment (5 micrograms/ml) causes a decrease in Ca2+ content within minutes, possibly by raising the intracellular concentration of free Ca2+ and thus stimulating its efflux. The response of Ca2+ content to ionophore concentration is biphasic, with low doses causing a decrease and high doses an increase. The sparing effect of Mg2+ on Ca2+-dependent killing of cells by the ionophore suggests that the ionophore kills cells by increasing the cytoplasmic concentration of free Ca2+, thereby creating a competition between Ca2+ and Mg2+ for certain Mg2+-requiring reactions needed for cell survival.