Estrogen acutely inhibits ion transport by isolated stria vascularis.

We investigated the nongenomic effects of female sex steroid hormones on the short circuit current (I(sc,probe)) across gerbil stria vascularis using the voltage-sensitive vibrating probe. The strial marginal cell epithelial layer produces I(sc,probe) by secreting K+ via I(Ks) channels in the apical membrane. Application of 17beta-estradiol (E2) caused a decrease of I(sc,probe) in a dose-dependent manner (10 nM-10 microM) within seconds. Tamoxifen, a competitive inhibitor of the intracellular estrogen receptor, did not change the inhibitory effect of E2. Activation of I(Ks) channels by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid in the presence and absence of E2 was used to test the mechanism of action. The results were consistent with a direct inhibitory effect of E2 on the I(Ks) channels. By contrast, progesterone caused a transient increase of I(sc,probe). These results suggest that E2 decreases secretion of K+ by inhibition of I(Ks) channels via a nongenomic mechanism at concentrations near those occurring under some physiologic conditions while progesterone caused only transient effects on I(sc,probe).