Ouabain-Stimulated Trafficking Regulation of the Na/K-ATPase and NHE3 in Renal Proximal Tubule Cells

Document Type


Publication Date

Spring 5-23-2012


We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase a1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the a1 subunit and NHE3 as well as transcellular 22Na? transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig a1 was replaced by ouabain-resistant rat a1). Ouabain-induced inhibition of transcellular 22Na? transport is due to an ouabain-induced redistribution of the a1 subunit and NHE3. In LLC-PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3, but has no significant effect on recycling of endocytosed a1 subunit. These data indicated that the ouabain-induced redistribution of the a1 subunit and NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase signaling influences NHE3 regulation.


The final publication is available at http://link.springer.com/article/10.1007/s11010-012-1331-x#page-1. Copyright © 2012 Springer Science+Business Media. All rights reserved. DOI 10.1007/s11010-012-1331-x