Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis

Breiderhoff, T., Himmerkus, N., Stuiver, M., Mutig, K., Will, C., Meij, I. C., Bachmann, S., Bleich, Markus, Willnow, T. E. and Muller, D. (2012) Deletion of claudin-10 (Cldn10) in the thick ascending limb impairs paracellular sodium permeability and leads to hypermagnesemia and nephrocalcinosis Proceedings of the National Academy of Sciences, 109 (35). pp. 14241-14246. DOI 10.1073/pnas.1203834109.

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Abstract

In the kidney, tight junction proteins contribute to segment specific selectivity and permeability of paracellular ion transport. In the thick ascending limb (TAL) of Henle's loop, chloride is reabsorbed transcellularly, whereas sodium reabsorption takes transcellular and paracellular routes. TAL salt transport maintains the concentrating ability of the kidney and generates a transepithelial voltage that drives the reabsorption of calcium and magnesium. Thus, functionality of TAL ion transport depends strongly on the properties of the paracellular pathway. To elucidate the role of the tight junction protein claudin-10 in TAL function, we generated mice with a deletion of Cldn10 in this segment. We show that claudin-10 determines paracellular sodium permeability, and that its loss leads to hypermagnesemia and nephrocalcinosis. In isolated perfused TAL tubules of claudin-10-deficient mice, paracellular permeability of sodium is decreased, and the relative permeability of calcium and magnesium is increased. Moreover, furosemide-inhibitable transepithelial voltage is increased, leading to a shift from paracellular sodium transport to paracellular hyperabsorption of calcium and magnesium. These data identify claudin-10 as a key factor in control of cation selectivity and transport in the TAL, and deficiency in this pathway as a cause of nephrocalcinosis.

Document Type: Article
Research affiliation: Kiel University
Kiel University > Kiel Marine Science
OceanRep > The Future Ocean - Cluster of Excellence
Refereed: Yes
DOI etc.: 10.1073/pnas.1203834109
ISSN: 0027-8424
Projects: Future Ocean
Date Deposited: 08 Mar 2017 10:46
Last Modified: 08 Mar 2017 10:46
URI: http://eprints.uni-kiel.de/id/eprint/36841

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