Estrogen receptor α mediates acute potassium channel stimulation in human coronary artery smooth muscle cells

The pleiotropic effects of estrogen are mediated via stimulation of two estrogen receptor ( ER) subtypes, ER alpha and ER beta. Although a number of studies have identified expression of one or both subtypes in estrogen target tissues, fewer studies have correlated ER expression with a functional role of these proteins in regulating cellular excitability. In the present study, we have combined cellular fluorescence, immunocytochemistry, and molecular expression techniques with single-channel patch-clamp studies to determine which ER mediates estrogen-stimulated potassium channel activity in human coronary artery smooth muscle cells ( HCASMC). We had demonstrated previously that estrogen stimulates activity of the large-conductance, calcium- and voltage-activated potassium ( BKCa) channel in HCASMC via a nongenomic mechanism. We now demonstrate expression of both ER alpha and ER beta subtypes in HCASMC. Functionally, however, expression of ER alpha antisense plasmid abolished the acute effect of estrogen on these channels, whereas estrogen retained its ability to stimulate BKCa channels in cells transfected with only green fluorescence protein. In contrast, overexpression of ER alpha enhanced the stimulatory action of estrogen in HCASMC. Transfection with ER beta antisense/sense plasmid did not alter ER beta expression. These findings indicate that the ER beta isoform mediates estrogen-induced stimulation of BKCa channels in HCASMC and thereby provide evidence for a receptor-dependent signaling mechanism that can mediate estrogen-induced inhibition of cellular excitability.