Critical role of the mineralocorticoid receptor in aldosterone-dependent and aldosterone-independent regulation of ENaC in the distal nephron
Viatcheslav Nesterov, Marko Bertog, Jérémie Canonica, Edith Hümmler, Richard A. Coleman, Paul A. Welling, Christoph Korbmacher
Abstract
Using a mouse model with inducible nephron-specific mineralocorticoid receptor (MR) deficiency, we demonstrated that MR is not only critical for maintaining aldosterone-dependent ENaC activity in CNT/CCD but also for aldosterone-independent ENaC activity in DCT2/CNT. Furthermore, we demonstrated that cells of this latter nephron segment express little 11β-HSD2, which probably allows glucocorticoids to stimulate MR, resulting in aldosterone-independent ENaC activity in DCT2/CNT. This site-specific ENaC regulation has physiologically relevant implications for renal sodium and potassium homeostasis.
Topics & Concepts
AldosteroneEpithelial sodium channelMineralocorticoid receptorMineralocorticoidEndocrinologyInternal medicineNephronHomeostasisReceptorKidneyChemistryBiologySodiumMedicineOrganic chemistryIon Transport and Channel RegulationHormonal Regulation and HypertensionElectrolyte and hormonal disorders