SEPARATE ROLES FOR CALCIUM AND MAGNESIUM IN THEIR SYNERGISTIC EFFECT ON URIDINE UPTAKE BY CULTURED-CELLS - SIGNIFICANCE FOR GROWTH-CONTROL

The uptake of uridine of 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. Change 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. The authors 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 of growth.