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

Mechanically induced intercellular Ca²⁺ waves propagated for approximately 300 μm in primary glial cultures. Following the wave propagation, 34% of the cells displayed Ca²⁺ oscillations in a zone 60–120 μm 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 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 Ca²⁺ wave into a distinct spatial and temporal pattern of Ca²⁺ oscillations. GLIA 28:97–113, 1999. © 1999 Wiley‐Liss, Inc.