Coupling between phosphate and calcium homeostasis: a mathematical model
Files
Accepted manuscript
Date
2017-12-01
Authors
Granjon, David
Bonny, Olivier
Edwards, Aurelie
Version
Accepted manuscript
OA Version
Citation
David Granjon, Olivier Bonny, Aurelie Edwards. 2017. "Coupling between phosphate and calcium homeostasis: a mathematical model." AMERICAN JOURNAL OF PHYSIOLOGY: RENAL PHYSIOLOGY, Volume 313, Issue 6, pp. F1181 - F1199. https://doi.org/10.1152/ajprenal.00271.2017
Abstract
Coupling between phosphate
and calcium homeostasis: a mathematical model. Am J Physiol Renal
Physiol 313: F1181–F1199, 2017. First published July 26, 2017;
doi:10.1152/ajprenal.00271.2017.—We developed a mathematical
model of calcium (Ca) and phosphate (PO4) homeostasis in the rat to
elucidate the hormonal mechanisms that underlie the regulation of Ca
and PO4 balance. The model represents the exchanges of Ca and PO4
between the intestine, plasma, kidneys, bone, and the intracellular
compartment, and the formation of Ca-PO4-fetuin-A complexes. It
accounts for the regulation of these fluxes by parathyroid hormone
(PTH), vitamin D3, fibroblast growth factor 23, and Ca2-sensing
receptors. Our results suggest that the Ca and PO4 homeostatic
systems are robust enough to handle small perturbations in the
production rate of either PTH or vitamin D3. The model predicts that
large perturbations in PTH or vitamin D3 synthesis have a greater
impact on the plasma concentration of Ca2 ([Ca2]p) than on that of
PO4 ([PO4]p); due to negative feedback loops, [PO4]p does not
consistently increase when the production rate of PTH or vitamin D3
is decreased. Our results also suggest that, following a large PO4
infusion, the rapidly exchangeable pool in bone acts as a fast, transient
storage PO4 compartment (on the order of minutes), whereas the
intracellular pool is able to store greater amounts of PO4 over several
hours. Moreover, a large PO4 infusion rapidly lowers [Ca2]p owing
to the formation of CaPO4 complexes. A large Ca infusion, however,
has a small impact on [PO4]p, since a significant fraction of Ca binds
to albumin. This mathematical model is the first to include all major
regulatory factors of Ca and PO4 homeostasis.