Major intracellular cations and growth control: Correspondence among magnesium content, protein synthesis, and the onset of DNA synthesis in BALB/c3T3 cells

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Abstract
Omission of Ca2+ from the medium of confluent BALB/c3T3 cells for a period of 17 h causes a large decrease in the number of cells synthesizing DNA. This effect is reversed by raising the Mg2+ concentration of the medium to 20 mM; if the [Mg2+] is > 20 mM (ultrahigh Mg2+), there is again a decrease in the number of cells synthesizing DNA. The synthesis of protein has a similar dependence on Mg2+ concentration in Ca2+-deficient medium, but it responds within 45 min of the shift in cation concentrations rather than the 10 h that is required for the change in DNA synthesis to become apparent. Cells in the ultrahigh Mg2+ concentrations that are at first inhibitory to protein synthesis later return to maximal protein synthesis. This delayed increase in protein synthesis is reflected in a delayed increase in DNA synthesis. Intracellular concentrations of Mg2+ in Ca2+-deficient media increase in proportion to extracellular Mg2+ concentrations. Cells in medium with 30 mM Mg2+ have a high intracellular content of Mg2+ at 3 h but have decreased their intracellular content by 17 h, a time at which protein synthesis has been restored to normal. Intracellular Na+ and K+ concentrations also change in Ca2+-deficient medium, but independent variation of these ions shows that protein synthesis is relatively insensitive to their concentration. Intracellular Ca2+ remains fairly constant under all these conditions. The rate of protein synthesis of intact cells changes as a function of intracellular Mg2+ content in a manner very similar to that which has been reported for cell-free systems. Protein synthesis is very sensitive to small changes in intracellular [Mg2+] within physiological range and the onset of DNA synthesis is dependent on the rate of protein synthesis. Regulation of the availability of Mg2+ within the cell therefore presents a plausible mechanism for growth control.