ABSTRACT
A tight control of intracellular [Ca[Formula: see text]] is essential for the survival and normal function of cells. In this study we investigate key mechanistic steps by which calcium is regulated and calcium oscillations could occur using in silico modeling of membrane transporters. To do so we give a deterministic description of intracellular Ca[Formula: see text] dynamics using nonlinear dynamics in order to understand Ca[Formula: see text] signaling. We first present the ordinary differential equations (ODEs) system for cell calcium kinetics and make a preliminary work on Sobol indices. We then describe and analyze complex transporters action. Besides, we analyze the whole system. We finally perform numerical simulations and compare our results to real data.
Subject(s)
Calcium , Membrane Transport Proteins , Animals , Calcium/metabolism , Calcium Signaling/physiology , Computer SimulationABSTRACT
Regulation of renal proximal tubular reabsorption of phosphate (Pi) is one of the critical steps in Pi homeostasis. Experimental evidence suggests that this regulation is achieved mainly by controlling the apical expression of the Na+-dependent Pi cotransporter type IIa (NaPi-IIa) in proximal tubules. Only recently have we started to obtain information regarding the molecular mechanisms that control the apical expression of NaPi-IIa. The first critical observation was the finding that truncation of only its last three amino acid residues has a strong effect on apical expression. A second major finding was the observation that the last intracellular loop of NaPi-IIa contains sequence information that confers parathyroid hormone (PTH) sensitivity. The use of the above domains of the cotransporter in yeast two-hybrid (Y2H) screening allowed the identification of proteins interacting with NaPi-IIa. Biochemical and morphological, as well as functional, analyses have allowed us to obtain insights into the physiological roles of such interactions, although our present knowledge is still far from complete.
