Abstract
Aldosterone binds to the mineralocorticoid receptor (MR) and increases renal Na+ reabsorption via up-regulation of the epithelial Na+ channel (ENaC) and the Na+-K+-ATPase in the collecting system (CS) and possibly also via the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). However, whether aldosterone directly regulates NCC via MR or indirectly through systemic alterations remains controversial. We used mice with deletion of MR in ∼20 % of renal tubule cells (MR/X mice), in which MR-positive (MRwt) and -negative (MRko) cells can be studied side-by-side in the same physiological context. Adult MR/X mice showed similar mRNA and protein levels of renal ion transport proteins to control mice. In MR/X mice, no differences in NCC abundance and phosphorylation was seen between MRwt and MRko cells and dietary Na+ restriction up-regulated NCC to similar extent in both groups of cells. In contrast, MRko cells in the CS did not show any detectable alpha-ENaC abundance or apical targeting of ENaC neither on control diet nor in response to dietary Na+ restriction. Furthermore, Na+-K+-ATPase expression was unaffected in MRko cells of the DCT, while it was lost in MRko cells of the CS. In conclusion, MR is crucial for ENaC and Na+-K+-ATPase regulation in the CS, but is dispensable for NCC and Na+-K+-ATPase regulation in the DCT.
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Acknowledgments
The authors would like to thank Günter Schütz and Stefan Berger, Burkhard Becher, Celso E. Gomez-Sanchez, and Eric Feraille for kindly providing us with the MRlox/lox mouse line, the cmv-cre mouse line, the anti-MR antibodies, and the anti-Na+-K+-ATPase antibody, respectively. The expert technical assistance by Monique Carrel and Michèle Heidemeyer is gratefully acknowledged.
Grants
This work was supported by the Swiss National Centre for Competence in Research “Kidney.CH” and by a project grant (310030_143929/1) from the Swiss National Science Foundation. David Penton is a postdoctoral fellow of the Marie-Curie program within the European Union’s 7th Framework Program for Research, Technological Development and Demonstration under the grant agreement no. 608847.
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Czogalla, J., Vohra, T., Penton, D. et al. The mineralocorticoid receptor (MR) regulates ENaC but not NCC in mice with random MR deletion. Pflugers Arch - Eur J Physiol 468, 849–858 (2016). https://doi.org/10.1007/s00424-016-1798-5
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DOI: https://doi.org/10.1007/s00424-016-1798-5