Intercellular Ca 2+ waves induce temporally and spatially distinct intracellular Ca 2+ oscillations in glia

Mechanically induced intercellular Ca 2+ waves propagated for approximately 300 μm in primary glial cultures. Following the wave propagation, 34% of the cells displayed Ca 2+ oscillations in a zone 60–120 μm from the stimulated cell. The initiation, frequency, and duration of these Ca 2+ 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 Ca 2+ wave. When an individual cell propagated two sequential intercellular Ca 2+ waves originating from different sites, the characteristics of the Ca 2+ oscillations initiated by each wave were determined by the distance of the cell from the origin of each wave. Each Ca 2+ oscillation commonly occurred as an intracellular Ca 2+ wave that was initiated from a specific site within the cell. The position of the initiation site and the direction of the intracellular Ca 2+ wave were independent of the orientation of the initial intercellular Ca 2+ wave. Because initiation and frequency of Ca 2+ oscillations are dependent on the intracellular inositol trisphosphate concentration ([IP 3 ] i ), we propose that the zone of cells displaying Ca 2+ oscillations is determined by an intercellular gradient of [IP 3 ] i , established by the diffusion of IP 3 through gap junctions during the propagation of the intercellular Ca 2+ wave. Exposure to acetylcholine, a muscarinic agonist that initiates IP 3 production, shifted the zone of oscillating cells about 45 μm farther away from the origin of the mechanically induced wave. These findings indicate that a glial syncytium can resolve information provided by a local Ca 2+ wave into a distinct spatial and temporal pattern of Ca 2+ oscillations. GLIA 28:97–113, 1999. © 1999 Wiley‐Liss, Inc.