CALCIUM WAVES AND OSCILLATIONS DRIVEN BY AN INTERCELLULAR GRADIENT OFINOSITOL (1,4,5)-TRISPHOSPHATE

In response to a local mechanical stimulus, mixed glial cells initiall y exhibit a propagating intercellular Ca2+ wave. Subsequently, cells w ithin a zone, at a specific distance from the stimulated cell, display asynchronous intracellular Ca2+ oscillations. The experimental hypoth esis that the initial Ca2+ wave could be mediated by the passive diffu sion of inositol (1,4,5)-trisphosphate (IP3) from the stimulated cell has been verified by model simulations. Further simulations with the s ame model also show that Ca2+ oscillations can only occur within model cells when the IP3 concentration is within a specific range. Thus, th is passive diffusion model predicts (a) that the IP3 concentration gra dient established in the cells following mechanical stimulation will i nitiate Ca2+ oscillations in cells in a specific zone along this gradi ent and (b) that different Ca2+ oscillatory patterns will occur within a specified oscillatory zone. Both of these predictions have been con firmed by experimental data. The failure of experimentally observed Ca 2+ oscillations to approach synchrony or entrain indicates a low inter cellular calcium permeability of about 0.1 mu m/s, and further suggest s that Ca2+ does not appear to act as a significant messenger in the i nitiation of these intercellular Ca2+ waves or oscillations. In conclu sion a passive diffusion of IP3, but not Ca2+, through gap junctions r emains the preferred hypothesis for the mechanism underlying mechanica lly-stimulated intercellular calcium waves and Ca2+ oscillations. (C) 1998 Elsevier Science B.V. All rights reserved.