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

摘要

The uptake of uridine by BALB/c3T3 cells is markedly inhibited by reducing the concentration of Mg²⁺ in medium containing only traces of Ca²⁺. When physiological [Ca²⁺] is present in the medium, omission of Mg²⁺ has no effect on uridine uptake, and when Mg²⁺ is present, omission of Ca²⁺ has only a slight inhibitory effect. When both Ca²⁺ and Mg²⁺ are omitted, the concentration of Ca²⁺ in the cells is not reduced, but that of Mg²⁺ 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 Ca²⁺ alone is restored to the medium of cells that had been deprived of both Ca²⁺ and Mg²⁺, there is no increase in the greatly depressed rate of uridine uptake, but when Mg²⁺ alone is restored, the rate of uridine uptake returns to control values. We conclude that the omission of Ca²⁺ from the medium has no direct effect on uridine uptake, but acts by increasing the exchange of Mg²⁺ between cells and medium and by otherwise altering the availability of Mg²⁺ 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.