Increased Intercellular Communication in Mouse Astrocytes Exposed to Hyposmotic Shocks

摘要

When exposed to 20% and 35%, but not to 50% hyposmotic solutions, mouse astrocytes recovered their volume within a few minutes, which coincided with the activation of nonjunctional conductances. Conductance of gap junctions between astrocyte pairs also increased after exposure to a 35% hyposmotic shock; however, this effect began at 3 min after the shock, when cells had partially recovered their initial volumes. During the first minute of exposure to 20% and 35% hyposmotic stimuli, there was a transient monophasic increase in intracellular calcium levels; exposure to 50% hyposmotic solution led to intracellular Ca²⁺ oscillations. The differences in time courses of nonjunctional conductance changes, Ca²⁺ alterations, and intercellular coupling suggest that distinct second messenger pathways are involved in each response. The velocity of mechanically evoked calcium waves propagated among the astrocytes increased at 7.5 min after 35% hyposmotic shock. This increase was not seen with 20% or 50% hyposmotic stimuli and is not ascribable to the increase in junctional conductance because it was blocked by suramin, a P2 purinergic receptor antagonist. Given that the transduction pathways activated during cell swelling (e.g., generation of phospholipases, phosphokinases, arachidonic acid) exert inhibitory effects on astrocytic gap junctions (), it is proposed that the increased junctional conductance during hyposmotic shock is due to increased number of channels, perhaps triggered by the initial Ca²⁺ signals (). As a functional consequence of the increased coupling and enhanced extracellular propagation of Ca²⁺ waves, spread of signaling molecules throughout the glial network is expected to be significantly enhanced during hyposmotic stress. The increased intercellular communication between mouse astrocytes in response to hyposmotic challenge thus occurs via both gap junction-dependent and -independent mechanisms and presumably provides neuroprotective effects following nervous system injury