Magnesium reverses inhibitory effects of calcium deprivation on coordinate response of 3T3 cells to serum

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Abstract
Deprivation of Ca2+ in crowded cultures of [mouse embryo fibroblast] 3T3 cells inhibits the onset of DNA synthesis. By raising [Mg2+] to 15 mM the inhibition produced by Ca2+ deprivation can be fully overcome. Sparse cultures are not inhibited by a similar deprivation of Ca2+, and therefore are not stimulated by supranormal [Mg2+]. The time course of stimulation of the onset of DNA synthesis by supranormal [Mg2+] in low [Ca2+] is the same as that produced by serum in physiological concentrations of Ca2+ and Mg2+. Concentrations of Mg2+ > 20 mM in low [Ca2+] reverse the stimulation, and [Mg2+] .gtoreq. 30 mM kill many cells. In contrast to the stimulation by 15 mM Mg2+, supranormal [Ca2+] had no effect on the onset of DNA synthesis in cultures inhibited by Mg2+ deprivation, if the formation of insoluble Ca-Pi complexes is prevented. Neither Na+ nor K+ reproduces the effects of Mg2+. The uptake of uridine is another parameter of the coordinate response of 3T3 cells to serum stimulation that is inhibited by Ca2+ deprivation and supranormal [Mg2+] also reverses this inhibition. The coordinate response of growth and metabolism to external effectors is probably regulated by the availability of Mg2+ within the cell and the inhibitory effects of Ca2+ deprivation are indirect and caused by a reduction in the availability of Mg2+.

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