Separate roles for calcium and magnesium in their synergistic effect on uridine uptake by cultured cells: significance for growth control.

The uptake of uridine by BALB/c3T3 cells is markedly inhibited by reducing the concentration of Mg(2+) in medium containing only traces of Ca(2+). When physiological [Ca(2+)] is present in the medium, omission of Mg(2+) has no effect on uridine uptake, and when Mg(2+) is present, omission of Ca(2+) has only a slight inhibitory effect. When both Ca(2+) and Mg(2+) are omitted, the concentration of Ca(2+) in the cells is not reduced, but that of Mg(2+) is reduced to about one-half in 3 hr. The concentration of K(+) is also reduced, and that of Na(+) is increased, suggesting increased membrane permeability to cations. The rate of diffusion of the nontransported hexose, L-glucose, into the cells is greatly increased. Changes in intracellular Na(+) and K(+) concentrations do not in themselves affect uridine uptake. When Ca(2+) alone is restored to the medium of cells that had been deprived of both Ca(2+) and Mg(2+), there is no increase in the greatly depressed rate of uridine uptake, but when Mg(2+) alone is restored, the rate of uridine uptake returns to control values. We conclude that the omission of Ca(2+) from the medium has no direct effect on uridine uptake, but acts by increasing the exchange of Mg(2+) between cells and medium and by otherwise altering the availability of Mg(2+) for this reaction. A similar conclusion is reached in considering the role of these ions in the regulation of other reactions of the coordinate response, including the initiation of DNA synthesis and the control growth.