17beta-estradiol and tamoxifen regulate a maxi-chloride channel from human placenta.
Steroid hormones have been implicated in the modulation of several transport processes, including conductive chloride transport in epithelial cells. Micromolar concentrations of these hormones have been determined in blood of pregnant women. The purpose of this work was to explore the effects of 17beta-Estradiol, a steroid hormone, on the biophysical properties of the Maxi chloride channel present in apical membranes from human placental syncytiotrophoblast. Apical membrane chloride channels from human term placentas were reconstituted in giant liposomes suitable for electrophysiologic studies by the patch-clamp method. Low micromolar concentrations of 17beta-Estradiol inhibit the Maxi chloride channels in excised patches in a potential-dependent manner. The addition of 1 mM 17beta-Estradiol to the bath solution decreased the total current in the patch from 100% control to 71% at -40 mV holding potential and the current was not affected by 17beta-Estradiol at + 40 mV. However, the presence of the hormone did not affect the single-channel conductance, therefore its effect must be due to modulation of its open probability (Po). Interestingly, 17alpha-Estradiol did not change the total current in the patch. Tamoxifen, an antiestrogen, also showed inhibition, but in a voltage-independent manner. Our results suggest that the Maxi Cl- channel from human term placenta may be regulated by direct interaction of both compounds with the channel. From a functional point of view, the control of these channels by steroid hormones may be of great importance in placental physiology and their regulation may help to unravel their possible role in transplacental transport.
Henriquez
M
M
Programa de Fisiología y Biofisica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Casilla 70005, Santiago 7, Chile.
Riquelme
G
G
D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000187:drug effects* / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology
D018118:Chloride Channels; D008081:Liposomes; D013629:Tamoxifen; D004958:Estradiol