Sneyd, Tsaneva-Atanasova, Yule, Thompson, Shuttleworth, 2004

Model Status

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

Model Structure

In reponse to an increased concentration of inositol trisphoshate (IP3), oscillations in the concentration of intracellular Ca2+ occur in many different cell types where they play important regulatory roles of many cellular functions. Transmembrane Ca2+ transport is known to have a pronounced effect on these Ca2+ oscillations, however, controversy over the mechanisms underlying these effects exists. To further complicate the issue, the consequences of blocking membrane transport or inhibiting Ca2+ entry vary between different cell types. For example, in some cell types Ca2+ oscillations persist in the absence of Ca2+ entry, while in others oscillations depend on Ca2+ entry.

Using a combination of theoretical and experimental work, Sneyd et al. study these differences between cell types. They conclude that small changes in the total amount of Ca2+ in a cell have have a large effect on Ca2+ oscillations. The mathematical model which the authors develop (see the figure below) is based on a dynamic model of the IP3 receptor (also see A Dynamic Model of the Type-2 Inositol Triphosphate Receptor, 2002). The model predicts that the cell can be balanced at a point where small changes in the total amount of Ca2+ can move the cellinto or out of oscillatory regions, resulting in the appearance or disappearance of oscillations. Sneyd et al. make the conclusion that the role of Ca2+ entry during an oscillation is to replenish the total amount of Ca2+ in the cell.

The complete original paper reference is cited below:

Control of calcium oscillations by membrane fluxes, J. Sneyd, K. Tsaneva-Atanasova, D. I. Yule, J. L. Thompson, and T. J. Shuttleworth, 2004, PNAS , 101, 1392-1396. (Full text (HTML) and PDF versions of the article are available to subscribers on the PNAS website.) PubMed ID: 14734814

Schematic diagram of the calcium fluxes described by the mathematical model.