Developmentally regulated cell cycle dependence of swelling-activated anion channel activity in the mouse embryo

Anion channels activated by increased cell volume are a nearly ubiquitous m echanism of cell volume regulation, including in early preimplantation mous e embryos. Here, we show that the swelling-activated anion current (I-Cl,I- swell) in early mouse embryos is cell-cycle dependent, and also that this d ependence is developmentally regulated. I-Cl,I-swell is present both in fir st meiotic prophase (germinal vesicle stage) mouse oocytes and in unfertili zed mature oocytes in second meiotic metaphase, and it persists after ferti lization though the 1-cell and 2-cell stages. I-Cl,I-swell was found to rem ain unchanged during metaphase at the end of the 1-cell stage. However I-Cl ,I-swell decreased during prophase and became nearly undetectable upon entr y into metaphase at the end of the 2-cell stage. Entry into prophase/metaph ase was required for the decrease in I-Cl,I-swell at the end of the 2-cell stage, since it persisted indefinitely in 2-cell embryos arrested in late G (2). There is considerable evidence that the channel underlying I-Cl,I-swel l is not only permeable to inorganic anions, but to organic osmolytes as we ll. We found a similar pattern of cell cycle and developmental dependence i n the 1-cell and 2-cell stages for the swelling-induced increase in permeab ility to the organic osmolyte glycine. Thus, entry into metaphase deactivat es I-Cl,I-swell in embryos, but only after developmental progression throug h the 2-cell stage.