A model of calcium transport and regulation in the proximal tubule

American Journal of Physiology. Renal Physiology
Aurélie Edwards, Olivier Bonny

Abstract

The objective of this study was to examine theoretically how Ca2+ reabsorption in the proximal tubule (PT) is modulated by Na+ and water fluxes, parathyroid hormone (PTH), Na+-glucose cotransporter (SGLT2) inhibitors, and acetazolamide. We expanded a previously published mathematical model of water and solute transport in the rat PT (Layton AT, Vallon V, Edwards A. Am J Physiol Renal Physiol 308: F1343-F1357, 2015) that did not include Ca2+. Our results indicate that Ca2+ reabsorption in the PT is primarily driven by the transepithelial Ca2+ concentration gradient that stems from water reabsorption, which is itself coupled to Na+ reabsorption. Simulated variations in permeability or transporter activity elicit opposite changes in paracellular and transcellular Ca2+ fluxes, whereas a simulated decrease in filtration rate lowers both fluxes. The model predicts that PTH-mediated inhibition of the apical Na+/H+ exchanger NHE3 reduces Na+ and Ca2+ transport to a similar extent. It also suggests that acetazolamide- and SGLT2 inhibitor-induced calciuria at least partly stems from reduced Ca2+ reabsorption in the PT. In addition, backleak of phosphate (PO4) across tight junctions is predicted to reduce net PO4 reabsorption by ~20% unde...Continue Reading

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Citations

Jun 21, 2018·American Journal of Physiology. Renal Physiology·Alan M Weinstein
Nov 24, 2018·Diabetes/metabolism Research and Reviews·Evangelia KalaitzoglouKathryn M Thrailkill
Mar 7, 2019·American Journal of Physiology. Renal Physiology·Joshua N Curry, Alan S L Yu
Apr 9, 2019·Current Opinion in Nephrology and Hypertension·Joanna Sophia J VinkeMartin H de Borst
Sep 1, 2019·Journal of Cellular and Molecular Medicine·Franca AnglaniJohn Lieske
Mar 22, 2020·International Journal of Molecular Sciences·Allein PlainR Todd Alexander
Feb 21, 2019·American Journal of Physiology. Renal Physiology·Aurélie EdwardsOlivier Bonny
Oct 28, 2019·American Journal of Physiology. Renal Physiology·Aurélie Edwards, Alicia A McDonough
Nov 27, 2019·JBMR Plus·Giuseppe CiancioloGaetano La Manna
Mar 20, 2021·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Yusuke BabaFumitaka Okajima
Apr 3, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Mallory L Downie, R Todd Alexander
Nov 15, 2019·Morphologie : Bulletin De L'Association Des Anatomistes·S Randall Thomas

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Methods Mentioned

BETA
gene knockout

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