The role of intracellular Cl‐ concentration in cell proliferation

Modulation of ion permeability during the cell cycle is one of the key events in cell cycle progression. Our recent study indicates that intracellular Cl− concentration ([Cl−]i) could act as a signal to regulate ion channel mRNA expression in renal epithelial A6 cells (AJP 287:F932‐9, 2004). This result suggests that the changes of [Cl−]i is one of the important candidates to cell proliferation. In the present study, we studied whether [Cl−]i regulates cell proliferation in A6 cells. Treatment with low Cl− (about 15 mM) medium (replacement of NaCl by NaNO3) for 72 h induce a significant decrease of [Cl−]i associated with reduction of cell growth rate compared with control (normal Cl− medium). Using flow cytometrical analysis, we found that cell cycle arrest occurred at the G0/G1 phase in low Cl−‐treated cells. These data indicate that [Cl−]i plays important roles in cell proliferation and cell cycle transition through the G1/S checkpoint. This work was supported by Grants‐in‐Aid from JSPS (17390057, 17590191, 17790154).