A three dimensional model of intercellular calcium signaling in epithelial cells

Abstract

Nature has designed a highly regulated system for the transport of ions and small molecules across the epithelial barrier that separates the surfaces of the body from the external environment. These systems contain regulatory elements controlled by external and internal signals. In order to understand the complexity of these systems, we have developed a fully three-dimensional model of calcium signaling in epithelial cells. The model is based on a set of reaction diffusion equations that are solved on a large-scale finite-element code in three dimensions. We have explicitly included the major compartments in the cell (i.e. the nucleus and endoplasmic reticulum). The model allows for buffering of free Ca/sup 2+/, calcium induced calcium release (CICR), and for the explicit inclusion of mobile buffers, mimicking the dyes used in the experiments. Additionally we have considered intercellular transport by including a realistic representation of the gap junctions that have a significant effect on the Ca/sup 2+/ wave propagation. In order to make quantitative comparisons to experimental results, we have used fluorescence microscopy images of cell tissue to generate an accurate mesh. Using this realistic geometry, we present results for the Ca/sup 2+/ wave propagation through the tissue as a function of both initial conditions used to start the wave and various geometrical parameters which affect propagation such as gap junction density and distribution, and presence of nuclei.