Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells.
Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current decreased in G1 and increased in early S phase, compared to that in G0. The isotonic steady-state current, which seems to be predominantly VRAC, also decreased in G1, and increased again in early S phase, to a level similar to that in G0. In contrast, the maximal CaCC current (500 nM free Ca2+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude.
Klausen
Thomas Kjaer
TK
Department of Biochemistry, Institute for Molecular Biology and Physiology, University of Copenhagen, Copenhagen, Denmark.
Bergdahl
Andreas
A
Hougaard
Charlotte
C
Christophersen
Palle
P
Pedersen
Stine F
SF
Hoffmann
Else K
EK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002224:Carbanilides; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D009995:Osmosis / Q000502:physiology; D018408:Patch-Clamp Techniques; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D002224:Carbanilides; D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D014508:Urea; C517730:NS-3728; D002118:Calcium