Volume-activated chloride channels in HeLa cells are blocked by verapamil and dideoxyforskolin

Pflugers Arch. 1993 Jan;422(4):347-53. doi: 10.1007/BF00374290.


The possible role of Cl- currents in regulatory volume decrease processes has been explored in HeLa cells using the whole-cell recording mode of the patch-clamp technique. Cells showed very small currents in voltage-clamp experiments performed with Cl(-)-rich, permeant-cation-free (N-methyl-D-glucamine replacement) intracellular and bathing solutions. Exposure of the cells to hypotonic solutions visibly swelled the cells and activated, reversibly, an outward rectifying Cl- current, which decayed at the most depolarised voltages used. Replacement of extracellular Cl- by a series of halide anions, SCN- and gluconate was consistent with an anion selectivity sequence: SCN- > I- > Br- > Cl- > F- > gluconate. The volume-regulated Cl- current was effectively inhibited by 100 microM 5-nitro-2-(3-phenyl-propylamino)-benzoic acid and by 100 microM 4,4'-diisothiocyanotostilbene-2,2-disulphonic acid, substances known to block Cl- channels in a variety of cells. Chloride current activation by hypotonicity was dependent on the presence of ATP in the intracellular solution and this requirement could be replaced by the non-hydrolysable analogue ATP[gamma S] and Mg(2+)-free ATP. The data suggest that the channels responsible for the current described are involved in the regulatory volume decrease in HeLa cells. The characteristics of this Cl- current are similar to those of the current associated with expression of multidrug resistance P-glycoprotein. Furthermore, the currents in HeLa cells were inhibited rapidly and reversibly by verapamil and 1,9-dideoxyforskolin, which are known to inhibit P-glycoprotein function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / physiology
  • Chloride Channels
  • Chlorides / metabolism*
  • Colforsin / analogs & derivatives*
  • Colforsin / pharmacology
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • HeLa Cells / physiology
  • Humans
  • Hypotonic Solutions
  • Ion Channels / drug effects*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Proteins / drug effects*
  • Osmosis
  • Verapamil / pharmacology*


  • Chloride Channels
  • Chlorides
  • Hypotonic Solutions
  • Ion Channels
  • Membrane Proteins
  • Colforsin
  • Adenosine Triphosphate
  • Verapamil
  • 1,9-dideoxyforskolin