Collecting duct–specific gene inactivation of αENaC in the mouse kidney does not impair sodium and potassium balance
Isabelle Rubera, … , Edith Hummler, Bernard C. Rossier
Isabelle Rubera, … , Edith Hummler, Bernard C. Rossier
Published August 15, 2003
Citation Information: J Clin Invest. 2003;112(4):554-565. https://doi.org/10.1172/JCI16956.
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Article Nephrology

Collecting duct–specific gene inactivation of αENaC in the mouse kidney does not impair sodium and potassium balance

Abstract

Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the α subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance.

Authors

Isabelle Rubera, Johannes Loffing, Lawrence G. Palmer, Gustavo Frindt, Nicole Fowler-Jaeger, Daniel Sauter, Tom Carroll, Andrew McMahon, Edith Hummler, Bernard C. Rossier

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Figure 4

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Transition of CNT to CCD in the kidney of Scnn1aloxloxCre and Scnn1aloxl...
Transition of CNT to CCD in the kidney of Scnn1aloxloxCre and Scnn1aloxlox mice kept on a sodium-free diet for 6 days. (a) Immunofluorescence on consecutive cryosections with rabbit antibodies against αENaC and AQP2. Bright apical αENaC immunofluorescence ceases abruptly at the transition from CNT to CCD (arrows). AQP2 is seen in CNT and CCD. AQP2-negative cells in CNT and CCD are intercalated cells; the weak, punctuate staining in some tubular cells was not localized at the apical membrane, was occasionally observed with the αENaC antibody, and is nonspecific. P, proximal tubule. Scale bar, ∼20 μm. (b) Immunofluorescent detection of CB, NCX, and αENaC on consecutive cryosections from kidneys of loxlox (control) and loxloxCre (experimental) mice. In mice of both genotypes, the sharp transition from CNT to CCD (arrows) is characterized by a drop of cytoplasmic CB immunostaining and a breakoff, i.e., discontinuity, of basolateral NCX abundance. In the Scnn1aloxlox mouse, apical αENaC immunostaining continues from the CNT to the CCD, whereas in Scnn1aloxlox mice, αENaC immunoreactivity is seen in CNT but not CCD. Scale bar, 20 μm.