Sex differences in the effects of β‐estradiol on ENaC current in cell culture

Abstract

Using cell‐attached patch clamp, we have previously shown that β‐estradiol (E2) activates epithelial sodium channels (ENaC) in alveolar cells. In an attempt to develop a high throughput electrophysiological assay to test the effect of estradiol (E2) and estrogen receptor agonists/antagonists on ENaC, we examined the effect of E2 on amiloride‐sensitive transepithelial current (TEC) in two kidney cell lines (2F3 and mpkccd) with known ENaC activity. E2 had no effect on amiloride sensitive current in either of these cell lines. The lack of an E2 response in the 2F3 and mpkccd cells may result from differences in tissue origin (lung vs. kidney) or sex of the donor animal (male for 2F3 and mpkccd cells, female for L2 cells). To address this question, we measured TEC in MDCK cells, a kidney cell line from a female dog. E2 increased amiloride‐sensitive TEC in MDCK cells. These data suggest that E2 increases ENaC current in females only and may play a role in sex differences in the rate and severity of diseases involving ENaC.Funding: NIH R37DK037963, K12GM000680 and T32HL076118