Fink, Slepchenko, Loew, 1999

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Intracellular calcium dynamics are frequently the subject of theoretical mathematical models (De Young and Keizer, 1992, Li and Rinzel, 1994, Keizer and Levine, 1996, Jafri-Rice-Winslow, 1998, and Snyder et al., 2000 are just a few examples of calcium dynamic models that have been coded up into CellML). The physical and chemical laws of calcium waves and oscillations can be expressed in terms of differential equations describing reaction kinetics, fluxes through membranes, and diffusion.

Inositol-1,4,5-triphosphate (IP3)-mediated calcium release from the endoplasmic reticulum is an important intracellular signalling mechanism in many cell types. In their 1999 study, Fink et al. determine the levels of IP3 required for calcium release in A7r5 cells (a rat smooth muscle cell from the thoracic aorta). Experimental data were used to construct a mathematical model of the IP3-dependent calcium changes (see the figure below). This model considers of several elements, including:

  • the mechanism of the IP3-receptor;

  • IP3 degradation;

  • calcium buffering in the cytosol;

  • and
  • refilling of the endoplasmic reticulum (ER) calcium stores via sarcoplasmic endoplasmic reticulum ATPase (SERCA) pumps.

The calcium response to IP3 release and its subsequent degradation were modelled using Vitual Cell software. By combining experimental and modelling approaches, IP3 and Ca2+ time courses can be directly compared.

Determination of Time-Dependent Inositol-1,4,5-Trisphosphate Concentrations during Calcium Release in a Smooth Muscle Cell, Charles C. Fink, Boris Slepchenko, and Leslie M. Loew, 1999, Biophysical Journal , 77, 617-628. (Full text and PDF versions of the article are available to subscribers on the Biophysical Journal website.) PubMed ID: 10388776