Calcium waves and oscillations driven by an intercellular gradient of inositol (1,4,5)-trisphosphate

Abstract

In response to a local mechanical stimulus, mixed glial cells initially exhibit a propagating intercellular Ca2+ wave. Subsequently, cells within a zone, at a specific distance from the stimulated cell, display asynchronous intracellular Ca2+ oscillations. The experimental hypothesis that the initial Ca2+ wave could be mediated by the passive diffusion of inositol (1,4,5)-trisphosphate (IP3) from the stimulated cell has been verified by model simulations. Further simulations with the same model also show that Ca2+ oscillations can only occur within model cells when the IP3 concentration is within a specific range. Thus, this passive diffusion model predicts (a) that the IP3 concentration gradient established in the cells following mechanical stimulation will initiate Ca2+ oscillations in cells in a specific zone along this gradient and (b) that different Ca2+ oscillatory patterns will occur within a specified oscillatory zone. Both of these predictions have been confirmed by experimental data. The failure of experimentally observed Ca2+ oscillations to approach synchrony or entrain indicates a low intercellular calcium permeability of about 0.1 micron/s, and further suggests that Ca2+ does not appear to act as a significant messenger in the initiation of these intercellular Ca2+ waves or oscillations. In conclusion a passive diffusion of IP3, but not Ca2+, through gap junctions remains the preferred hypothesis for the mechanism underlying mechanically-stimulated intercellular calcium waves and Ca2+ oscillations.