Correlated effects of external magnesium on cation content and DNA synthesis in cultured chicken embryo fibroblasts

Depletion of Mg 2+ in the growth medium for chicken embryo fibroblasts produces a large decrease in DNA synthesis as measured by 3 H‐thymidine incorporation, and concomitant decreases in cellular K + and Mg 2+ and increases in Na + and Ca 2+ . In cells grown in media containing 0.2 mM Ca 2+ , graded reduction of Mg 2+ from 0.8 mM (control) to 0.016 mM produced graded decreases in DNA synthesis to 10% of control at 0.016 mM Mg 2+ . Concomitantly, cell cations showed graded changes, Na + increasing to 227%, K + decreasing to 52.5%, Mg 2+ decreasing to 57.5% and Ca 2+ increasing to 153.5% of control. The effects of Mg 2+ depletion on DNA synthesis and cell cation content exhibited a dependence on Ca 2+ concentration, the effects being larger at low Ca 2+ concentration. Use of inorganic pyrophosphate in the growth medium as a selective complexor of Mg 2+ caused a marked decrease in DNA synthesis which was accompanied by changes in cellular cation content similar to those produced by direct Mg 2+ depletion. The effects of Mg 2+ depletion on cell cation content are explainable in terms of changes in membrane permeability caused by rapid external surface exchange of bound divalent cations. Among the several interpretations of the data in terms of possible mechanisms by which changes in external Mg 2+ concentration may affect cell metabolism, the most consistent with known properties of the system is the concept of a central role for intracellular free Mg 2+ in the coordinate control of growth and metabolism in animal cells.