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Am J Physiol Renal Physiol 291: F503-F508, 2006. First published March 22, 2006; doi:10.1152/ajprenal.00482.2005
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Redistribution of distal tubule Na+-Cl cotransporter (NCC) in response to a high-salt diet

Monica B. Sandberg,1 Arvid B. Maunsbach,2 and Alicia A. McDonough1

1Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California; and 2The Water and Salt Research Center, Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus C, Denmark

Submitted 5 December 2005 ; accepted in final form 7 March 2006

ABSTRACT

The distal convoluted tubule (DCT) apical Na+-Cl cotransporter (NCC) is responsible for the reabsorption of 5–10% of filtered NaCl and is the target for thiazide diuretics. NCC abundance is increased during dietary NaCl restriction and by aldosterone and decreased during a high-salt (HS) diet and mineralocorticoid blockade. This study tested the hypothesis that subcellular distribution of NCC is also regulated in response to changes in dietary salt. Six-week-old Sprague-Dawley rats were fed a normal-salt diet (NS; 0.4% NaCl) for 3 wk, then switched to a HS diet (4% NaCl) for 3 wk or a low-salt diet (LS; 0.07% NaCl) for 1 wk. Under anesthesia, kidneys were excised, renal cortex was dissected, and NCC was analyzed with specific antibodies after either 1) density gradient centrifugation followed by immunoblotting or 2) fixation followed by immunoelectron microscopy. The HS diet decreased NCC abundance to 0.50 ± 0.10 of levels in LS diet (1.00 ± 0.23). The HS diet also caused a redistribution of NCC from low to higher density membranes. Immunoelectron microscopy revealed that NCC resides predominantly in the apical membrane in rats fed the LS diet and increases in subapical vesicles in rats fed the HS diet. In conclusion, a HS diet provokes a rapid and persistent redistribution of NCC from apical to subapical membranes, a mechanism that would facilitate a homeostatic decrease in NaCl reabsorption in the DCT to compensate for increased dietary salt.

sodium transport; distal convoluted tubule; dietary salt; thiazide receptor



Address for reprint requests and other correspondence: A. A. McDonough, Dept. of Physiology and Biophysics, Univ. of Southern California Keck School of Medicine, 1333 San Pablo St., MMR 626, Los Angeles, CA 90089-9142 (e-mail: mcdonoug{at}usc.edu)




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