A role for chloride permeability in the regulation of the extracellular fluid volume
(1997)
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- Quantitatively, the reabsorption of NaCl and water represents the major function of the nephrons. The bulk of the filtered Na+ is reasbsorbed by the proximal tubule, Henle’s loop and distal tubule. Although its contribution to total reabsoprtion is small, the Na+ reabsorption which takes place in the collecting duct (the most distal portion of the nephron) is adjusted to maintain excretion at a level appropriate for dietary intake and, therefore, is critical to the preservation of an adequate Na+ balance and of an euvolemic state. Aldosterone is the primary hormonal regulator of collecting duct NA+ reabsorption and its stimulatory effect on Na+ transport by tubular cells is well documented. The electroneutrality of the extracellular fluid requires that Na+ reabsorption is paralleled by that of CI-; still, many questions are left concerning the mechanism(s) underlying Cl- permeability and its (their- regulation by aldosterone. <BR> The transepithelial CI- pathways has thus been characterized in aldosterone-responsive models of the mammalian collecting duct. Because of its unique properties in terms of salt and water reabsorption in Amphibia, we first used the amphibian skin epithelium to demonstrate that transepithelial Cl- permeability is conductive and stimulated by aldosterone, independently of NA+ transport. Further studies were performed on the skin of amphibians acclimated to selected environments as well as on monolayers from the amphibian A6 cell line. These studies led to the demonstration that acid-base regulation is linked to Cl- permeability, and that a specialized cell type in the amphibian skin epithelium (the mitochondria-rich cell, similar to the intercalated cell of the mammalian collecting duct) is involved in Cl- permeability. With immohistochemical studies and Western blot analyses, we subsequently demonstrated that a band 3-related protein, possibly involved in Cl- -HCO3-exchange, is expressed in the apical membrane of the mitochondria-rich cells, and might be the molecular basis for their involvement in Cl- permeability and acid-base regulation. We also characterized by similar methods the Madin-Darby canine kidney cell line, a proposed model for intercalated cells. <BR> Going from amphibian models to the human kidney, we have shown that the effect of aldosterone on Cl- channel, in the human kidney. Comparison of the expression patterns encountered during nephrogenesis, in adulthood and in the autosomal dominant polycystic kidney disease led to the proposal that Cl- -mediated fluid secretion might play an important role during nephrogenesis and be involved in cystogenesis
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Devuyst, O. (1997). A role for chloride permeability in the regulation of the extracellular fluid volume. https://hdl.handle.net/2078.5/111425