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Am J Physiol Renal Physiol 279: F459-F467, 2000;
0363-6127/00 $5.00
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Vol. 279, Issue 3, F459-F467, September 2000

Long-term regulation of renal Na-dependent cotransporters and ENaC: response to altered acid-base intake

Gheun-Ho Kim1, Stephen W. Martin2, Patricia Fernández-Llama1, Shyama Masilamani1, Randall K. Packer2, and Mark A. Knepper1

1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1603; and 2 Department of Biological Sciences, George Washington University, Washington, District of Columbia 20052

Increased systemic acid intake is associated with an increase in apical Na/H exchange in the renal proximal tubule mediated by the type 3 Na/H exchanger (NHE3). Because NHE3 mediates both proton secretion and Na absorption, increased NHE3 activity could inappropriately perturb Na balance unless there are compensatory changes in Na handling. In this study, we use semiquantitative immunoblotting of rat kidneys to investigate whether acid loading is associated with compensatory decreases in the abundance of renal tubule Na transporters other than NHE3. Long-term (i.e., 7-day) acid loading with NH4Cl produced large decreases in the abundances of the thiazide-sensitive Na-Cl cotransporter (TSC/NCC) of the distal convoluted tubule and both the beta - and gamma -subunits of the amiloride-sensitive epithelial Na channel (ENaC) of the collecting duct. In addition, the renal cortical abundance of the proximal type 2 Na-dependent phosphate transporter (NaPi-2) was markedly decreased. In contrast, abundances of the bumetanide-sensitive Na-K-2Cl cotransporter of the thick ascending limb and the alpha -subunit of ENaC were unchanged. A similar profile of changes was seen with short-term (16-h) acid loading. Long-term (7-day) base loading with NaHCO3 resulted in the opposite pattern of response with marked increases in the abundances of the beta - and gamma -subunits of ENaC and NaPi-2. These adaptations may play critical roles in the maintenance in Na balance when changes in acid-base balance occur.

sodium-proton exchange; sodium-potassium-2 chloride cotransport; distal convoluted tubule; collecting duct; amiloride-sensitive epithelial sodium channel


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