Open AccessαENaC-Mediated Lithium Absorption Promotes Nephrogenic Diabetes Insipidus
Author(s) -
Birgitte Mønster Christensen,
Annie Mercier Zuber,
Johannes Loffing,
Jean-Christophe Stehle,
Peter M.T. Deen,
Bernard C. Rossier,
Edith Hummler
Publication year - 2011
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2010070734
Subject(s) - nephrogenic diabetes insipidus , aquaporin 2 , epithelial sodium channel , endocrinology , medicine , polyuria , lithium (medication) , chemistry , vasopressin , homeostasis , knockout mouse , amiloride , sodium , receptor , diabetes mellitus , water channel , mechanical engineering , organic chemistry , engineering , inlet
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.