Estrogen modulates a large conductance chloride channel in cultured porcine aortic endothelial cells.

Estrogen is known to exert a protective effect on cardiovascular disease, but the mechanism for this effect is unclear. It has, however, been reported that estrogen and antiestrogen modify ionic currents and membrane potential in various cells. The aim of this study was to clarify whether the chloride channel of aortic endothelial cells was, in fact, modified by estrogen and antiestrogen with inside-out patch and cell-attached patch recording methods. Tamoxifen activated a large-conductance (368 +/- 23 pS, n = 6, in symmetric 150 mM Cl- solution) chloride channel of endothelial cells grown in the presence of 1 microg/ml colchicine. The channels were activated mainly between +/-40 mV, but were inactivated at more extreme potentials. The open probability of channels in cell-attached patches increased from <0.01 to 0.37 +/- 0.08 (n = 8) when cells were treated with 15 microM tamoxifen. This effect can be blocked by 17beta-estradiol, but not by progesterone. The results showed that tamoxifen increased chloride channel activity in the presence of colchicine in cultured endothelial cells, and this action was suppressed by 17beta-estradiol but not by progesterone. This rapid effect by estrogens suggests that these hormones exert nongenomic, short-term activity and do not appear to affect the nuclear estrogen receptor. With these effects, estrogen and antiestrogen bind to the endothelial cells plasma membrane site and subsequently may activate an intracellular second messenger pathway.