Intracellular univalent cations and the regulation of the BALB/c-3T3 cell cycle.

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Abstract
Addition of serum to density-arrested BALB/c-3T3 cells causes a rapid increase in uptake of Na+ and K+, followed 12 h later by the onset of DNA synthesis. The role of intracellular univalent cation concentrations in the regulation of BALB/c-3T3 cell growth by serum growth factors was eplored. As cells grew to confluence, intracellular Na+ and K+ concentrations ({Na+} and {K+}i) fell from 40 and 180 to 15 and 90 mmol/l, respectively. Stimulation of growth of density-inhibited cells by the addition of serum growth factors increased {Na}i by 30% and {K+}i by 13-25% in early G0/G1, resulting in an increase in total univalent cation concentration. Addition of ouabain to stimulated cells resulted in a concentration-dependent steady decrease in {K+}i and increase in {Na+}i. Ouabain (100 .mu.M) decreased {K+}i to .apprx. 60 mmol/l by 12 h, and also prevented the serum-stimulated increase in 86Rb uptake. However, 100 .mu.M ouabain did not inhibit DNA synthesis. A time-course experiment was done to determine the effect of 100 .mu.M ouabain on {K+}i throughout G0/G1 and S phase. The addition of serum growth factors to density-inhibited cells stimulated equal rates of entry into the S phase in the presence or absence of 100 .mu.M ouabain. In the presence of ouabain, there was a decrease in {K+}i. An increase in {K+}i is not required for entry into S phase; serum growth factors do not regulate cell growth by altering {K+}i. The significance of increased total univalent cation concentration is discussed.