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.
D000818:Animals; D000001:Calcimycin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002999:Clone Cells; D008274:Magnesium / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000001:Calcimycin; D008274:Magnesium; D002118:Calcium