VOLUME-ACTIVATED CHLORIDE CHANNELS IN NEUROBLASTOMA-CELLS ARE BLOCKEDBY THE ANTIESTROGEN TOREMIFENE

The presence of volume-activated chloride channels has been examined i n neuroblastoma C1300 cells using the whole-cell configuration of the patch-clamp technique, Chloride channels could not be detected under i sotonic conditions. However, hypotonic challenge induced slowly develo ped inward and outward anionic currents that exhibited outward rectifi cation and inactivation at the moist depolarizing potentials, features that were similar to the currents described in other cell preparation s where volume-activated Cl- channels have been associated with the ex pression of P-glycoprotein. This hypotonicity-activated Cl- currents c ould be reversibly blocked by extracellular exposure to toremifene, a novel synthetic antioestrogen. The fact that toremifene and its analog tamoxifen, have been shown to black P-glycoprotein-associated chlorid e channels and to reverse P-glycoprotein associated multidrug resistan ce in a number of cell lines suggest that P-glycoprotein could be invo lved in the generation of hypotomic-induced chloride conductance in ne uroblastoma cells.