Inhibition of voltage-gated cationic channels in rat embryonic hypothalamic neurones and C1300 neuroblastoma cells by triphenylethylene antioestrogens

The effect of the non-steroidal antioestrogens tamoxifen and toremifene on voltage-gated cationic currents was examined in primary cultures of rat hypothalamic neurones and the C1300 mouse neuroblastoma cell line using the whole-cell patch clamp technique. When applied to the external bathing solution both tamoxifen and toremifene were able to inhibit TTX-sensitive sodium currents with IC50 values of 1-2 mu M and delayed rectifier type potassium currents (IC50, 2-3 mu M), However, only toremifene showed a significant inhibition of the I-A current (IC50 3 mu M), Inhibition of voltage-gated cationic currents was significantly impaired when tamoxifen was applied in a serum-containing solution, The steroidal antioestrogen ICI 182,780 did not inhibit any of the currents at 10 mu M. (C) 1998 Federation of European Biochemical Societies.