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 videomicroscopy and the whole-cell patch clamp technique. Regulatory volume decrease (RVD) and volume-sensitive Cl- conductance (G(Cl,vol)) were measured: (1) in proliferating cells of different sizes; (2) in cells arrested in defined phases of the cell cycle (G1, G1/S, S, and M phases) using mevastatin, mimosine, hydroxyurea, aphidicolin, cytosine beta-D-arabinofuranoside, and taxol; and (3) in serum-starved cells (G(0) state). Cells in all groups were able to undergo RVD, although the cells approaching mitosis (i.e., the largest cells in proliferating cultures and the taxol-treated cells) had the lowest rates of shrinkage during RVD. In agreement with this finding, the density of G(Cl,vol) was stable in proliferating and cell cycle-arrested cells for most of the cell cycle, with the exception of the cells approaching mitosis and the new daughter cells where the density was decreased to half. The impairment of RVD was greatest in serum-starved cells which also had the lowest density of G(Cl,vol). We conclude that proliferating cells maintain an ability to recover from osmotic swelling as they progress through the cell cycle, although this ability may be compromised during mitosis.
Loeb Health Research Institute, Ottawa Hospital, University of Ottawa, 75 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9. pdoroshenko@lri.ca
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D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008898:Mimosine / Q000494:pharmacology; D009997:Osmotic Pressure; D017239:Paclitaxel / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D002712:Chlorides; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D003561:Cytarabine; C012258:mevastatin; D016590:Aphidicolin; D008898:Mimosine; D008148:Lovastatin; D017239:Paclitaxel; D006918:Hydroxyurea