Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells.
Patch-clamping and cell image analysis techniques were used to study the expression of the volume-activated Cl(-) current, I(Cl(vol)), and regulatory volume decrease (RVD) capacity in the cell cycle in nasopharyngeal carcinoma cells (CNE-2Z). Hypotonic challenge caused CNE-2Z cells to swell and activated a Cl(-) current with a linear conductance, negligible time-dependent inactivation, and a reversal potential close to the Cl(-) equilibrium potential. The sequence of anion permeability was I(-) > Br(-) > Cl(-) > gluconate. The Cl(-) channel blockers tamoxifen, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), and ATP inhibited I(Cl(vol)). Synchronous cultures of cells were obtained by the mitotic shake-off technique and by a double chemical-block (thymidine and hydroxyurea) technique. The expression of I(Cl(vol)) was cell cycle dependent, being high in G(1) phase, downregulated in S phase, but increasing again in M phase. Hypotonic solution activated RVD, which was cell cycle dependent and inhibited by the Cl(-) channel blockers NPPB, tamoxifen, and ATP. The expression of I(Cl(vol)) was closely correlated with the RVD capacity in the cell cycle, suggesting a functional relationship. Inhibition of I(Cl(vol)) by NPPB (100 microM) arrested cells in G(0)/G(1). The data also suggest that expression of I(Cl(vol)) and RVD capacity are actively modulated during the cell cycle. The volume-activated Cl(-) current associated with RVD may therefore play an important role during the cell cycle progress.
Chen
Lixin
L
School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, Wales, UK.
Wang
Liwei
L
Zhu
Linyan
L
Nie
Sihai
S
Zhang
Jin
J
Zhong
Ping
P
Cai
Bo
B
Luo
Haibing
H
Jacob
Tim J C
TJ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001965:Bromides / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005942:Gluconates / Q000494:pharmacology; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology; D007454:Iodides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010539:Permeability / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D001965:Bromides; D018118:Chloride Channels; D002712:Chlorides; D005942:Gluconates; D007038:Hypotonic Solutions; D007454:Iodides; D009579:Nitrobenzoates; D013629:Tamoxifen; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000255:Adenosine Triphosphate; C030691:gluconic acid