Okadaic acid-sensitive activation of Maxi Cl(-) channels by triphenylethylene antioestrogens in C1300 mouse neuroblastoma cells

J Physiol. 2001 Oct 1;536(Pt 1):79-88. doi: 10.1111/j.1469-7793.2001.00079.x.


1. The regulation of Maxi Cl(-) channels by 17beta-oestradiol and non-steroidal triphenylethylene antioestrogens represents a rapid, non-classical effect of these compounds. In the present study we have investigated the signalling pathways used for the regulation of Maxi Cl(-) channel activity by oestrogens and antioestrogens in C1300 neuroblastoma cells. 2. Whole-cell Maxi Cl(-) currents were readily and reversibly activated by tamoxifen, toremifene and the membrane-impermeant ethyl-bromide tamoxifen, only when applied to the extracellular medium. 3. Pre-treatment of C1300 cells with oestrogen or cAMP prevented the antioestrogen-induced activation of Maxi Cl(-) channels. The inhibitory effect of 17beta-oestradiol and cAMP was abolished by the kinase inhibitor staurosporine. 4. Current activation was unaffected by the removal of intracellular Ca(2+) and Mg(2+), but was completely abolished in the presence of okadaic acid. These results are consistent with the participation of an okadaic acid-sensitive serine/threonine protein phosphatase in the activation of Maxi Cl(-) channels. However, neither oestrogen or antioestrogen treatment modified the total activity of the two major serine/threonine phosphatases, PP1 and PP2A, in C1300 cells. 5. Although the role of these Maxi Cl(-) channels remains unknown, our findings suggest strongly that their modulation by oestrogens and antioestrogens is linked to intracellular signalling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / pharmacology*
  • Chloride Channels / metabolism*
  • Chlorides / metabolism
  • Cyclic AMP / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology
  • Mice
  • Neuroblastoma*
  • Okadaic Acid / pharmacology*
  • Patch-Clamp Techniques
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Selective Estrogen Receptor Modulators / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Staurosporine / pharmacology
  • Stilbenes / pharmacology*
  • Tamoxifen / pharmacology
  • Toremifene / pharmacology
  • Tumor Cells, Cultured


  • Carcinogens
  • Chloride Channels
  • Chlorides
  • Enzyme Inhibitors
  • Estrogen Antagonists
  • Selective Estrogen Receptor Modulators
  • Stilbenes
  • Tamoxifen
  • Okadaic Acid
  • Estradiol
  • Toremifene
  • Cyclic AMP
  • Phosphoprotein Phosphatases
  • Staurosporine
  • triphenylethylene