Membrane impermeant antioestrogens discriminate between ligand- and voltage-gated cation channels in NG108-15 cells

Biochim Biophys Acta. 2000 Dec 20;1509(1-2):229-36. doi: 10.1016/s0005-2736(00)00297-2.


Native 5-HT(3) and AChR ligand-gated cation channels can be inhibited (blocked) by the non-steroidal antioestrogen tamoxifen. However, the exact site and mechanism of inhibition by tamoxifen on these channels remain unclear. We have investigated the action of the membrane impermeant quaternary derivative, ethylbromide tamoxifen (EBT), on native ligand-gated 5-HT(3) receptor channels and voltage-gated K(+) channels in NG108-15 cells using whole cell patch clamp. Extracellular EBT inhibited whole cell cationic currents of 5-HT(3) receptors with IC(50) of 0.22+/-0.4 microM (n(H)=1.05+/-0.2). The channel block was characterised by voltage independent and use independent behaviour (similar to that of tamoxifen). EBT was unable to inhibit voltage-gated K(+) currents in NG108-15 cells. This was in contrast to the inhibition by tamoxifen which, at similar concentrations, accelerated the apparent inactivation of these outward K(+) currents. The inhibition of 5-HT(3) receptors by a membrane impermeant derivative of tamoxifen supports the view that the binding site for antioestrogens is extracellular and the inhibition is not mediated through genomic/transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane Permeability
  • Estrogen Receptor Modulators / pharmacology*
  • Hybrid Cells
  • Ion Channel Gating*
  • Ion Channels / antagonists & inhibitors*
  • Ligands
  • Mice
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects
  • Rats
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists / pharmacology
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured


  • Estrogen Receptor Modulators
  • Ion Channels
  • Ligands
  • Potassium Channels
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Tamoxifen