Intercellular Ca2+ waves induce temporally and spatially distinct intracellular Ca2+ oscillations in glia

Mechanically induced intercellular Ca2+ waves propagated for approximately 300 mu m in primary glial cultures. Following the wave propagation, 34% of the cells displayed Ca2+ oscillations in a zone 60-120 mu m from the stimulated cell. The initiation, frequency, and duration of these Ca2+ oscillations were dependent on the cells' distance from the wave origin but were not dependent on the cell type nor on the magnitude of the Ca2+ wave. When an individual cell propagated two sequential intercellular Ca2+ waves originating from different sites, the characteristics of the Ca2+ oscillations initiated by each wave were determined by the distance of the cell from the origin of each wave. Each Ca2+ oscillation commonly occurred as an intracellular Ca2+ wave that was initiated from a specific site within the cell. The position of the initiation site and the direction of the intracellular Ca2+ wave were independent of the orientation of the initial intercellular Ca2+ wave. Because initiation and frequency of Ca2+ oscillations are dependent on the intracellular inositol trisphosphate concentration ([IP3](i)), we propose that the zone of cells displaying Ca2+ oscillations is determined by an intercellular gradient of [IP3](i), established by the diffusion of IP3 through gap junctions during the propagation of the intercellular Ca2+ wave. Exposure to acetylcholine, a muscarinic agonist that initiates IP3 production, shifted the zone of oscillating cells about 45 mu m farther away from the origin of the mechanically induced wave. These findings indicate that a glial syncytium can resolve information provided by a local Ca2+ wave into a distinct spatial and temporal pattern of Ca2+ oscillations. (C) 1999 Wiley-Liss, Inc.