Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts

Cell cycle-related changes in the ability to regulate cell volume following hyposmotic swelling were studied in mouse fibroblasts using videomicroscop y and the whole-cell patch clamp technique. Regulatory volume decrease (RVD ) and volume-sensitive Cl- conductance (G(Cl,vol)) were measured: (1) in pr oliferaring cells of different sizes; (2) in cells arrested in defined phas es of the cell cycle (G(1),G(1)/S, S, and M phases) using mevastatin, mimos ine, hydroxyurea, aphidicolin, cytosine beta -D-arabinofuranoside, and taxo l; and (3) in serum-starved cells (G(0) state). Cells in all groups were ab le to undergo RVD, although the cells approaching mitosis (i.e., the larges t cells in proliferating cultures and the taxol-treated cells) had the lowe st rates of shrinkage during RVD. In agreement with this finding, the densi ty or G(Cl,vol) was stable in proliferating and cell cycle-arrested cells f or most of the cell cycle, with the exception of the cells approaching mito sis and the new daughter cells where the density was decreased to hair. The impairment of RVD was greatest in serum-starved cells which also had the l owest density of G(Cl,vol). We conclude that proliferating cells maintain a n ability to recover from osmotic swelling as they progress through the cel l cycle, although this ability may be compromised during mitosis. (C) 2001 Wiley-Liss, Inc.