Mathematical modelling of calcium wave propagation in mammalian airway epithelium: evidence for regenerative ATP release.

Airway epithelium has been shown to exhibit intracellular calcium waves after mechanical stimulation. Two classes of mechanism have been proposed to explain calcium wave propagation: diffusion through gap junctions of the intracellular messenger inositol 1,4,5-trisphosphate (IP3), and diffusion of paracrine extracellular messengers such as ATP. We have used single cell recordings of airway epithelium to parameterize a model of an airway epithelial cell. This was then incorporated into a spatial model of a cell culture where both mechanisms for calcium wave propagation are possible. It is shown that a decreasing return on the radius of Ca2+ wave propagation is achieved as the amount of ATP released from the stimulated cell increases. It is therefore shown that for a Ca2+ wave to propagate large distances, a significant fraction of the intracellular ATP pool would be required to be released. Further to this, the radial distribution of maximal calcium response from the stimulated cell does not produce the same flat profile of maximal calcium response seen in experiential studies. This suggests that an additional mechanism is important in Ca2+ wave propagation, such as regenerative release of ATP from cells downstream of the stimulated cell.