Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells

Am J Physiol Cell Physiol. 2002 Oct;283(4):C1313-23. doi: 10.1152/ajpcell.00182.2002.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Antineoplastic Agents, Hormonal / pharmacology
  • Bromides / pharmacology
  • Carcinoma / drug therapy
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Division / drug effects
  • Cell Size / drug effects
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / metabolism*
  • Chlorides / metabolism*
  • Gluconates / pharmacology
  • Humans
  • Hypotonic Solutions / pharmacology
  • Iodides / pharmacology
  • Membrane Potentials / drug effects
  • Nasopharyngeal Neoplasms / drug therapy
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nitrobenzoates / pharmacology
  • Patch-Clamp Techniques
  • Permeability / drug effects
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Hormonal
  • Bromides
  • Chloride Channels
  • Chlorides
  • Gluconates
  • Hypotonic Solutions
  • Iodides
  • Nitrobenzoates
  • Tamoxifen
  • 5-nitro-2-(3-phenylpropylamino)benzoic acid
  • Adenosine Triphosphate
  • gluconic acid