Cytoplasmic pH and the regulation of the Dictyostelium cell cycle.

Cytoplasmic pH (pHi) was monitored during the cell cycle of synchronous populations of Dictyostelium discoideum by means of a pH "null point" method. There is a cycle of pHi that closely corresponds to the DNA replication cycle, with a minimum of pH 7.20 in interphase and a peak of pH 7.45 during S phase and mitosis. When DNA replication is blocked by hydroxyurea, pHi continues to oscillate with a similar period as the uninhibited division cycle. Even when protein synthesis is inhibited by cycloheximide the periodic pHi cycles persist. Artificially raising pHi in exponentially growing cells by approximately 0.1 units causes a severalfold increase in the rates of protein and DNA synthesis. We conclude that an autonomous pHi oscillator exists in Dictyostelium cells, which operates independently of protein and DNA synthesis and which may have a major role in the timing and regulation of the cell cycle.