αENaC mediated lithium absorption promotes nephrogenic diabetes insipidus

Mønster Christensen, Birgitte; Mercier Zuber, Annie; Loffing, Johannes; Stehle, Jean-Christophe; Deen, Peter M.T.; Rossier, Bernard C.; Hummler, Edith

doi:10.1681/ASN.2010070734

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Journal article

αENaC mediated lithium absorption promotes nephrogenic diabetes insipidus

Mønster Christensen, Birgitte Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland - Water and Salt Research Center, Department of Anatomy, Aarhus University, Denmark
Mercier Zuber, Annie Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland
Loffing, Johannes Department of Medicine-Anatomy, University of Fribourg, Switzerland
Stehle, Jean-Christophe Departments of Pathology, University of Lausanne, Switzerland
Deen, Peter M.T. Department of Physiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
Rossier, Bernard C. Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland
Hummler, Edith Departments of Pharmacology and Toxicology, University of Lausanne, Switzerland

04.11.2010

Published in:

Journal of the American Society of Nephrology. - 2011, vol. 22, no. 2, p. 253-261

English Lithium-induced nephrogenic diabetes insipidus (NDI) is accompanied by polyuria, downregulation of aquaporin 2 (AQP2), and cellular remodeling of the collecting duct (CD). The amiloride-sensitive epithelial sodium channel (ENaC) is a likely candidate for lithium entry. Here, we subjected transgenic mice lacking αENaC specifically in the CD (knockout [KO] mice) and littermate controls to chronic lithium treatment. In contrast to control mice, KO mice did not markedly increase their water intake. Furthermore, KO mice did not demonstrate the polyuria and reduction in urine osmolality induced by lithium treatment in the control mice. Lithium treatment reduced AQP2 protein levels in the cortex/outer medulla and inner medulla (IM) of control mice but only partially reduced AQP2 levels in the IM of KO mice. Furthermore, lithium induced expression of H⁺-ATPase in the IM of control mice but not KO mice. In conclusion, the absence of functional ENaC in the CD protects mice from lithium-induced NDI. These data support the hypothesis that ENaC-mediated lithium entry into the CD principal cells contributes to the pathogenesis of lithium-induced NDI.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

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