INTERCELLULAR CALCIUM WAVES MEDIATED BY DIFFUSION OF INOSITOL TRISPHOSPHATE - A 2-DIMENSIONAL MODEL

In response to mechanical stimulation of a single cell, airway epithelial cells in culture exhibit a wave of increased intracellular free Ca2+ concentration that spreads from cell to cell over a limited distance through the culture. We present a detailed analysis of the intercellular wave in a two-dimensional sheet of cells. The model is based on the hypothesis that the wave is the result of diffusion of inositol trisphosphate (IP3) from the stimulated cell. The two-dimensional model agrees well with experimental data and makes the following quantitative predictions: as the distance from the stimulated cells increases, 1) the intercellular delay increases exponentially, 2) the intracellular wave speed decreases exponentially, and 3) the arrival time increases exponentially. Furthermore, 4) a proportion of the cells at the periphery of the response will exhibit waves of decreased amplitude, 5) the intercellular membrane permeability to IP3 must be similar to 2 mu m/s or greater, and 6) the ratio of the maximum concentration of IP3 in the stimulated cell to the K-m of the IP3 receptor (with respect to IP3) must be similar to 300 or greater. These predictions constitute a rigorous test of the hypothesis that the intercellular Ca2+ waves are mediated by IP3 diffusion.