SUPPRESSION OF ATP-INDUCED CL−SECRETION BY ENHANCED EXPRESSION OF EPITHELIAL NA+CHANNELS IN MOUSE ENDOMETRIAL EPITHELIUM

Abstract

We have studied the effect of enhanced expression of epithelial Na+channels (ENaC) on the ATP-induced Cl−secretion in the mouse epithelium using short-circuit current (ISC) and RT-PCR techniques. The amiloride sensitivity of basal current (Ib) across the cultured endometrial epithelia was found to vary with the magnitude of the Ib, the higher the Ibthe greater its sensitivity to amiloride, indicating possible elevation of ENaC. However, the magnitude of ATP-induced ISC, previously demonstrated to be mediated by Ca2+-activated chloride channel (CaCC), decreased as the amiloride sensitivity of the Ibincreased, suggesting a possible inhibitory effect of elevated expression of ENaC on ATP-mediated chloride secretion. The Matrigel treatment for culturing the endometrial epithelia affected the amiloride sensitivity of the Ibas well as the ATP-induced ISCreversedly. Competitive RT-PCR demonstrated that the expression of both ENaC γ subunits and CaCC was enhanced in Matrigel-treated cultures. However, the observed reduction in the ATP-induced or CaCC-mediated ISCcould not be explained by the CaCC expression pattern. These data suggest that inhibition of CaCC function is due to enhanced ENaC expression. Therefore, in addition to interacting with CFTR, ENaC also appears to interact with CaCC in the mouse endometrial epithelium. Physiologically the present findings indicate that enhanced expression of ENaC leads to suppression of other Cl−channels, such as CFTR and CaCC, thereby preconditioning the endometrium in favour of overall salt and water absorption as observed during embryo implantation.