A model of calcium transport and regulation in the proximal tubule.

Details

Serval ID
serval:BIB_BB498C093222
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A model of calcium transport and regulation in the proximal tubule.
Journal
American journal of physiology. Renal physiology
Author(s)
Edwards A., Bonny O.
ISSN
1522-1466 (Electronic)
ISSN-L
1522-1466
Publication state
Published
Issued date
01/10/2018
Peer-reviewed
Oui
Volume
315
Number
4
Pages
F942-F953
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The objective of this study was to examine theoretically how Ca <sup>2+</sup> reabsorption in the proximal tubule (PT) is modulated by Na <sup>+</sup> and water fluxes, parathyroid hormone (PTH), Na <sup>+</sup> -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 Ca <sup>2+</sup> . Our results indicate that Ca <sup>2+</sup> reabsorption in the PT is primarily driven by the transepithelial Ca <sup>2+</sup> concentration gradient that stems from water reabsorption, which is itself coupled to Na <sup>+</sup> reabsorption. Simulated variations in permeability or transporter activity elicit opposite changes in paracellular and transcellular Ca <sup>2+</sup> fluxes, whereas a simulated decrease in filtration rate lowers both fluxes. The model predicts that PTH-mediated inhibition of the apical Na <sup>+</sup> /H <sup>+</sup> exchanger NHE3 reduces Na <sup>+</sup> and Ca <sup>2+</sup> transport to a similar extent. It also suggests that acetazolamide- and SGLT2 inhibitor-induced calciuria at least partly stems from reduced Ca <sup>2+</sup> reabsorption in the PT. In addition, backleak of phosphate (PO <sub>4</sub> ) across tight junctions is predicted to reduce net PO <sub>4</sub> reabsorption by ~20% under normal conditions. When transcellular PO <sub>4</sub> transport is substantially reduced by PTH, paracellular PO <sub>4</sub> flux is reversed and contributes significantly to PO <sub>4</sub> reabsorption. Furthermore, PTH is predicted to exert an indirect impact on PO <sub>4</sub> reabsorption via its inhibitory action on NHE3. This model thus provides greater insight into the mechanisms that modulate Ca <sup>2+</sup> and PO <sub>4</sub> reabsorption in the PT.
Keywords
calcium, kidney, mathematical model, parathyroid hormone, phosphate
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation / Projects / 310030-163340
Create date
31/05/2018 16:42
Last modification date
17/09/2020 8:14
Usage data