Intracellular K+ and the mitogenic response of 3T3 cells to peptide factors in serum-free medium.

The stimulation of DNA synthesis in cultures of Swiss 3T3 cells by vasopressin, epidermal growth factor, and insulin added in serum-free medium is strikingly dependent on the intracellular K+ content or concentration. The relationship between these parameters is sigmoid; DNA synthesis commences only when the intracellular K+ increases above a certain threshold level (0.56 mumol/mg of protein; 90 mM). Addition of K+ to K+- depleted cultures reverses the block on DNA synthesis after a lag period of at least 8 hr. The sigmoid dependence of DNA synthesis on intracellular K+ is generated in early G1 phase rather than at the G1/S boundary. The effects of K+ on the G1-S transition are, at least in part, exerted through its control of protein synthesis. In serum-free medium, the K+ content is close to the threshold required for allowing a mitogenic response. The findings suggest that a small change in the intracellular K+ level can influence the ability of these cells to initiate DNA synthesis in serum-free medium.