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Sexual Dimorphic Expression of Renal Claudins, Water Channels and Transporters accounts for the Downstream Shift in Salt and Volume Reabsorption along the Nephron in Female vs. Male Rats
Author(s) -
Veiras Luciana Cecilia,
Pei Lei,
Yu Alan S.L.,
McDonough Alicia Ann
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.967.29
Subject(s) - paracellular transport , endocrinology , medicine , reabsorption , claudin , epithelial sodium channel , chemistry , apical membrane , aldosterone , distal convoluted tubule , cotransporter , sodium , kidney , biology , tight junction , permeability (electromagnetism) , biochemistry , membrane , organic chemistry
Recently, we reported that female rats, as well as mice, have lower abundance of apical proximal tubule (PT) sodium transporters (NHE3, NaPi2) as well as lower abundance of myosin VI, the motor that drives regulated redistribution of the apical transporters. This reduction in PT transporters in females is complemented by higher abundance and phosphorylation of distal tubule Na‐Cl cotransporter (NCC) and higher abundance of cleaved (activated) forms of epithelial sodium channels’ (ENaC) alpha and gamma subunits. At the physiologic level, the impact of the differences is evident as more rapid excretion of a saline load, higher clearance rate of endogenous lithium (a marker of flow from the proximal tubule), and no difference in thiazide sensitive natriuresis in females vs. males. The aim of the current study was to test the hypothesis that a sexual dimorphism in claudins (Cld‐) and water channels (AQP‐) accompanies the observed differences in transporters. Sprague Dawley rats were fasted overnight with water provided before termination. Abundance of claudins and water channels were determine by quantitative immunoblot of cortical or medullary homogenates. Claudin‐2 , expressed from the PT through the thin descending limb, forms high‐conductance cation‐selective paracellular pores that play an important role in the paracellular reabsorption of salt in the PT (>32% of the filtered load). Claudin‐2 expression in cortex was lower in females vs. males: 0.32 ± 0.03 vs. 1.0 ± 0.1 (p< 0.002). Aquaporin 1 , which confers “leakiness” to the PT, expressed in both apical and basolateral membranes of the PT, was also lower in females vs. males: 37 kD band: 0.44 ± 0.014 vs. 1.0 ± 0.023; 25 kD band: 0.84 ± 0.22 vs. 1.0 ± 0.26 (both p<0.001). Claudin‐7, expressed in the DCT and CCD, functions as either a Cl − barrier or pore; in vivo knockout provokes lethal salt wasting. Claudin‐7 expression in cortex was higher in females vs. males: 1.4 ± 0.01 vs. 1.0 ± 0.03 (p< 0.001). Claudin‐10 , detected all along the nephron, and medullary apical Aquaporin‐2 were expressed at similar levels in females and males. Conclusions Lower abundance of both Cld‐2 and AQP‐1 in females corresponds to lower Na + transporter abundance in the proximal nephron and may contribute to their improved ability to excrete a saline load. These factors may contribute to the lower blood pressures and resistance to experimental hypertension in females vs. males. In the distal nephron, higher abundance of Cld‐7 corresponds to the higher NCC and ENaC activities where it may facilitate salt reabsorption in response to the increased volume flow from the proximal nephron. Support or Funding Information AHA 15GRNT23160003 and NIH DK083785