Renal expression of parvalbumin is critical for NaCl handling and response to diuretics
- Belge, Hendrica Departments of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
- Gailly, Philippe Departments of Physiology, Université Catholique de Louvain Medical School, Brussels, Belgium
- Schwaller, Beat Unit of Anatomy, University of Fribourg, Switzerland
- Loffing, Johannes Unit of Anatomy, University of Fribourg, Switzerland
- Debaix, Huguette Departments of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
- Riveira-Munoz, Eva Departments of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
- Beauwens, Renaud Laboratory of Cell and Molecular Physiology, Université Libre de Bruxelles Medical School, Brussels, Belgium
- Devogelaer, Jean-Pierre Departments of Rheumatology, Université Catholique de Louvain Medical School, Brussels, Belgium
- Hoenderop, Joost G. Department of Physiology, Radboud University Nijmegen, The Netherlands
- Bindels, René J. Department of Physiology, Radboud University Nijmegen, The Netherlands
- Devuyst, Olivier Departments of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
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05.09.2007
Published in:
- Proceedings of the National Academy of Sciences of the United States of America. - 2007, vol. 104, no. 37, p. 14849-14854
English
The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca²⁺-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice (Pvalb–/–) vs. wild-type (Pvalb+/+) littermates. PV colocalized with the thiazide-sensitive Na⁺-Cl⁻ cotransporter (NCC) in the early DCT. The Pvalb–/– mice showed increased diuresis and kaliuresis at baseline with higher aldosterone levels and lower lithium clearance. Acute furosemide administration increased diuresis and natriuresis/kaliuresis, but, surprisingly, did not increase calciuria in Pvalb–/– mice. NaCl supplementation of Pvalb–/– mice increased calciuria at baseline and after furosemide. The Pvalb–/– mice showed no significant diuretic response to hydrochlorothiazide, but an accentuated hypocalciuria. A decreased expression of NCC was detected in the early DCT of Pvalb–/– kidneys in the absence of ultrastructural and apoptotic changes. The PV-deficient mice had a positive Ca²⁺ balance and increased bone mineral density. Studies in mouse DCT cells showed that endogenous NCC expression is Ca²⁺-dependent and can be modulated by the levels of PV expression. These results suggest that PV regulates the expression of NCC by modulating intracellular Ca²⁺ signaling in response to ATP in DCT cells. They also provide insights into the Ca²⁺-sparing action of thiazides and the pathophysiology of distal tubulopathies.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Médecine
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 8477
- DOI 10.1073/pnas.0702810104
- Persistent URL
- https://folia.unifr.ch/unifr/documents/300617
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