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Functional Implications of Sexual Dimorphism of Transporter Patterns along the Rat Nephron
Author(s) -
Hu Rui,
McDonough Alicia A,
Layton Anita
Publication year - 2019
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.2019.33.1_supplement.864.1
Subject(s) - nephron , reabsorption , cotransporter , medicine , endocrinology , sexual dimorphism , transporter , chemistry , kidney , apical membrane , renal physiology , tubule , water transport , biology , sodium , membrane , biochemistry , water flow , gene , organic chemistry , environmental engineering , engineering
The goal of this study is to investigate the functional implications of the sexual dimorphism in transporter patterns along the rodent nephron as reported by Veiras et al. (J Am Soc Nephrol 2018). To do so, we developed sex‐specific computational models of water and solute transport from Bowman space to the papillary tip of a superficial nephron of the kidneys of the male and female rats. The models account for the sex differences in expression levels of the apical and basolateral transporters, in single‐nephron glomerular filtration rate, and in tubular dimensions. Model simulations predict that ~70 and 40% of the filtered volume is reabsorbed by the proximal tubule of the male and female rat kidneys, respectively. The lower fractional volume reabsorption in the female rat can be attributed to their smaller transport area and lower aquaporin‐1 expression level. The latter also results in a larger contribution of the paracellular pathway to water transport. Similar fractions of the filtered Na + are reabsorbed by the male and female proximal tubule models, respectively. The lower fractional Na + reabsorption in female is due primarily to their smaller transport area, lower Na + /H + ‐exchanger (NHE3) activity, and lower claudin‐2 abundance. This results in significantly larger delivery of water and Na + to the downstream nephron segments in female. Unlike in the proximal tubule, the distal nephron of the female rat exhibits higher expression levels in key Na + transporters, including Na + ‐K + ‐Cl − cotransporter, Na + ‐Cl − cotransporter, and epithelial Na + channel. Not only do the higher expression levels of these transporters account for the enhanced water and Na + transport along the female distal nephron, relative to male, but they may also contribute to the female rat's ability to excrete a saline load more rapidly than male. Support or Funding Information This research was supported by the Canada 150 Research Chair program and by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .