Volume-activated chloride channels in neuroblastoma cells are blocked by the antiestrogen toremifene.
The presence of volume-activated chloride channels has been examined in neuroblastoma C1300 cells using the whole-cell configuration of the patch-clamp technique. Chloride channels could not be detected under isotonic conditions. However, hypotonic challenge induced slowly developed inward and outward anionic currents that exhibited outward rectification and inactivation at the most depolarizing potentials, features that were similar to the currents described in other cell preparations where volume-activated Cl- channels have been associated with the expression of P-glycoprotein. This hypotonicity-activated Cl- currents could be reversibly blocked by extracellular exposure to toremifene, a novel synthetic antioestrogen. The fact that toremifene and its analog tamoxifen, have been shown to block P-glycoprotein-associated chloride channels and to reverse P-glycoprotein associated multidrug resistance in a number of cell lines suggest that P-glycoprotein could be involved in the generation of hypotonic-induced chloride conductance in neuroblastoma cells.
Díaz
M
M
Departamento de Biología Animal, Facultad de Biología, Universidad de La Laguna, Tenerife, Spain.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D048429:Cell Size; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D018408:Patch-Clamp Techniques; D013629:Tamoxifen / Q000494:pharmacology; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018118:Chloride Channels; D002712:Chlorides; D004965:Estrogen Antagonists; D009419:Nerve Tissue Proteins; D013629:Tamoxifen; D017312:Toremifene; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid