Modeling local and global intracellular calcium responses mediated by diffusely distributed inositol 1,4,5-trisphosphate receptors

Journal of Theoretical Biology
George S B WilliamsGregory D Smith

Abstract

Considerable insight into intracellular Ca2+ responses has been obtained through the development of whole cell models that are based on molecular mechanisms, e.g., single channel kinetics of the inositol 1,4,5-trisphosphate (IP3) receptor Ca2+ channel. However, a limitation of most whole cell models to date is the assumption that IP3 receptor Ca2+ channels (IP3Rs) are globally coupled by a "continuously stirred" bulk cytosolic [Ca2+], when in fact open IP3Rs experience elevated "domain" Ca2+ concentrations. Here we present a 2N+2-compartment whole cell model of local and global Ca2+ responses mediated by N=100,000 diffusely distributed IP3Rs, each represented by a four-state Markov chain. Two of these compartments correspond to bulk cytosolic and luminal Ca2+ concentrations, and the remaining 2N compartments represent time-dependent cytosolic and luminal Ca2+ domains associated with each IP3R. Using this Monte Carlo model as a starting point, we present an alternative formulation that solves a system of advection-reaction equations for the probability density of cytosolic and luminal domain [Ca2+] jointly distributed with IP3R state. When these equations are coupled to ordinary differential equations for the bulk cytosolic and ...Continue Reading

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Citations

Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·Geneviève DupontJames W Putney
Oct 5, 2010·HFSP Journal·Geneviève Dupont, Huguette Croisier
Oct 2, 2009·Chaos·Geneviève Dupont, Laurent Combettes
Feb 2, 2016·Journal of Molecular and Cellular Cardiology·Andrew P WescottGeorge S B Williams
Sep 8, 2010·Mathematical Biosciences·Weijiu LiuJingvoon Chen
Mar 8, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Geneviève Dupont
Jun 3, 2008·Biophysical Journal·Geneviève DupontLaurent Combettes
Jan 1, 2013·Plants·Teresa Vaz MartinsRichard J Morris
Oct 7, 2017·PLoS Computational Biology·Agne TilūnaitėRüdiger Thul
May 3, 2014·Cold Spring Harbor Protocols·Rüdiger Thul

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