title: Effects of K+-deficient diets with and without NaCl supplementation on Na+, K+, and H2O transporters' abundance along the nephron.
abstract: Dietary potassium (K(+)) restriction and hypokalemia have been reported to change the abundance of most renal Na(+) and K(+) transporters and aquaporin-2 isoform, but results have not been consistent. The aim of this study was to reexamine Na(+), K(+) and H(2)O transporters' pool size regulation in response to removing K(+) from a diet containing 0.74% NaCl, as well as from a diet containing 2% NaCl (as found in American diets) to blunt reducing total diet electrolytes. Sprague-Dawley rats (n = 5-6) were fed for 6 days with one of these diets: 2% KCl, 0.74% NaCl (2K1Na, control chow) compared with 0.03% KCl, 0.74% NaCl (0K1Na); or 2% KCl, 2%NaCl (2K2Na) compared with 0.03% KCl, 2% NaCl (0K2Na, Na(+) replete). In both 0K1Na and 0K2Na there were significant decreases in: 1) plasma [K(+)] (<2.5 mM); 2) urinary K(+) excretion (<5% of control); 3) urine osmolality and plasma [aldosterone], as well as 4) an increase in urine volume and medullary hypertrophy. The 0K2Na group had the lowest [aldosterone] (172.0 ± 17.4 pg/ml) and lower blood pressure (93.2 ± 4.9 vs. 112.0 ± 3.1 mmHg in 2K2Na). Transporter pool size regulation was determined by quantitative immunoblotting of renal cortex and medulla homogenates. The only differences measured in both 0K1Na and 0K2Na groups were a 20-30% decrease in cortical β-ENaC, 30-40% increases in kidney-specific Ste20/SPS1-related proline/alanine-rich kinase, and a 40% increase in medullary sodium pump abundance. The following proteins were not significantly changed in both the 0 K groups: Na(+)/H(+) exchanger isoform 3; Na(+)-K(+)-Cl(-) cotransporter; Na(+)-Cl(-) cotransporter, oxidative stress response kinase-1; renal outer medullary K(+) channel; autosomal recessive hypercholesterolemia; c-Src, aquaporin 2 isoform; or renin. Thus, despite profound hypokalemia and renal K(+) conservation, we did not confirm many of the changes that were previously reported. We predict that changes in transporter distribution and activity are likely more important for conserving K(+) than changes in total abundance.
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
authors.forename: Mien T X
authors.initials: MT
authors.lastname: Nguyen
authors.forename: Li E
authors.initials: LE
authors.lastname: Yang
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Fletcher
authors.forename: Donna H
authors.initials: DH
authors.lastname: Lee
authors.forename: Hetal
authors.initials: H
authors.lastname: Kocinsky
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.forename: Eric
authors.initials: E
authors.lastname: Delpire
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011191:Potassium Deficiency / Q000378:metabolism*; D017419:Potassium, Dietary / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D017419:Potassium, Dietary; D017673:Sodium Chloride, Dietary; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters