Ion Channels – Membrane Transport – Integrative Physiology
Kidney International (2005) 67, 1868–1877; doi:10.1111/j.1523-1755.2005.00285.x
Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells
SANKARIDRUG M PERIYASAMY, JIANG LIU, FERAS TANTA, BESHER KABAK, BRENT WAKEFIELD, DEEPAK MALHOTRA, DAVID J KENNEDY, ALAA NADOOR, OLGA V FEDOROVA, WILLIAM GUNNING, ZIJIAN XIE, ALEXEI Y BAGROV and JOSEPH I SHAPIRO
Department of Medicine, Medical College of Ohio, Toledo, Ohio; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland; and Department of Pathology and Department of Pharmacology, Medical College of Ohio, Toledo, Ohio
Correspondence: Joseph I. Shapiro, M.D., Chairman, Department of Medicine, Medical College of Ohio, 3120 Glendale Avenue, Toledo, OH 43614–5089. E-mail: jshapiro@mco.edu
Received 14 March 2004; Revised 8 July 2004; Re-revised 5 November 2004; Re-revised 9 December 2004; Accepted 14 December 2004.
Abstract
Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells.
Background
We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells. The current report addresses the potential relevance of plasmalemmal Na/K-ATPase redistribution to in vivo salt handling.
Methods
Male Sprague-Dawley rats were given 1 week of a high salt (4.0% NaCl) or normal salt (0.4% NaCl) diet. Urinary sodium excretion, as well as MBG excretion, was monitored, and proximal tubules were isolated using a Percoll gradient method. Tubular 86Rb uptake, Na/K-ATPase enzymatic activity, and Na/K-ATPase 
1 subunit density were determined.
Results
The high salt diet increased urinary sodium (17.8 
1.8 vs. 2.5 0.3 mEq/day, P < 0.01) and MBG excretion (104 12 vs. 26 4 pmol/day), and decreased proximal tubular 86Rb uptake (0.44 0.07 vs. 1.00 0.10, P < 0.01) and Na/K-ATPase enzymatic activity (5.1 1.1 vs. 9.9 1.6 
mol/mg pr/hr, P < 0.01) relative to the normal diet. Proximal tubular Na/K-ATPase 1 protein density was decreased in the plasmalemma fraction but increased in both early and late endosomes following the high salt diet. In rats fed a high salt diet, anti-MBG antibody caused a 60% reduction in urinary sodium excretion, substantial increases in proximal tubule 86Rb uptake, and Na/K-ATPase enzymatic activity, as well as significant decreases in the early and late endosomal Na/K-ATPase 1 protein content.
Conclusion
These data suggest that redistribution of the proximal tubule Na/K-ATPase in response to endogenous cardiotonic steroids plays an important role in renal adaptation to salt loading.
Keywords:
sodium, potassium, Na+/K+-ATPase, endocytosis, hypertension
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