Effect of ouabain on growth regulation by serum components in Balb/C‐3T3 cells: Inhibition of entry into s phase by decreased protein synthesis

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Abstract
The effect of inhibition of the cell membrane Na+‐K+ pump on the Balb/c‐3T3 cell growth cycle was studied. Inhibition of the Na+‐K+ pump resulted in a dose‐dependent reduction of intracellular K+ concentration ({K+}i). However, inhibition of protein synthesis in G0/G1 and of subsequent entry into S phase occurred only after {K+}i fell below a critical threshold (50–60 mmoles/liter). Thus, when the {K+}i falls below a critical threshold, protein synthesis is inhibited, preventing cells from entering the S phase. The platelet‐derived growth factor (PDGF) induces cells to become “competent” to traverse the cell cycle; the platelet‐poor plasma component of serum allows competent cells to progress through G0/G1 and enter S phase. Inhibition of the Na+‐K+ pump did not prevent the induction of competence by PDGF, but it did reversibly inhibit plasma‐mediated events in early G0/G1. Similarly, cycloheximide inhibited plasma‐mediated events but did not prevent PDGF‐induced competence. Thus, protein synthesis may not be required for induction of competence; alternatively, the induction of the competent state may occur in these cells after removal of PDGF and protein synthesis inhibitor. Protein synthesis is required for subsequent plasma‐mediated events in G0/G1.