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Am J Physiol Renal Physiol 279: F252-F258, 2000;
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Vol. 279, Issue 2, F252-F258, August 2000

Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets

Johannes Loffing1, Laurence Pietri2, Fintan Aregger1, May Bloch-Faure2, Urs Ziegler1, Pierre Meneton2, Bernard C. Rossier3, and Brigitte Kaissling1

1 Institute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland; 2 Institut National de la Santé et de la Recherche Médicale U367, F-75005 Paris, France; and 3 Institut de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland

Previous electrophysiological experiments on renal cortical collecting ducts indicated that dietary sodium intake and variations in aldosterone plasma levels regulate the abundance of functional epithelial Na channels (ENaC) in the apical plasma membrane. In mouse kidney we investigated by immunohistochemistry whether feeding for 3 wk a diet with high (3% Na) and low (0.05% Na) Na content influences the distribution pattern of ENaC. In mice of all experimental groups, ENaC was apparent in cells from the late portion of the distal convoluted tubule (DCT2) down to the medullary collecting duct (CD). In mice on a high-Na diet (plasma aldosterone: 40.8 ± 2.0 ng/dl), the alpha -subunit was undetectable, and the beta - and gamma -ENaC were detected in the cytoplasm, but not in the apical plasma membrane of the cells. In contrast, in mice on a low-Na diet (plasma aldosterone: 93.6 ± 9.3 ng/dl) all three ENaC subunits were displayed in the subapical cytoplasm and in the apical membrane of DCT2, connecting tubule (CNT), and, although less prominent, in cortical CD cells. Apical plasma membrane immunostaining progressively decreased along the cortical CD, simultaneously with increasing cytoplasmic staining for beta - and gamma -ENaC. Thus our data on mice adapted to moderately low and high Na intake suggest that regulation of ENaC function in vivo involves shifts of beta - and gamma -subunits from the cytoplasm to the apical plasma membrane and vice versa, respectively. The insertion of these subunits into the apical plasma membrane coincides with upregulation of the alpha -subunit and its insertion into the apical plasma membrane.

aldosterone; trafficking; immunohistochemistry; distal nephron; sodium transport


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