Previous reports have shown that mechanically stimulated astrocytes release ATP. In this review, we describe the mechanisms of an increase in intracellular Ca2+ concentration in stimulated astrocytes after receiving ATP in an autocrine fashion and those of intercellular communication among astrocytes by Ca2+ propagation. We used astrocytes cultured from the cerebral cortices that were isolated from rat embryos. First, we found two different Ca2+ pathways in stimulated astrocytes. ATP received by purine receptors in an autocrine fashion primarily activates a cascade including G-protein, phospholipase C and inositol-1,4,5-trisphosphate, resulting in intracellular Ca2+ mobilization. The other Ca2+ system in astrocytes acts via a Ca2+ influx from the extracellular space. Second, to elucidate a mechanism of ATP release from stimulated astrocytes, we analyzed the elasticity of astrocytes by atomic force microscopy. The most important contribution to the cell membrane elasticity comes from actin filaments, because the membrane above actin filaments is always stiffer than the surroundings. A possible mechanism of ATP release in stimulated astrocytes may be, therefore, coupled to the deformation of actin filaments. Third, we analyzed the intercellular communication by Ca2+ propagation. Colocalization of connexin and filamentous actin was observed in the regions of cell-to-cell adhesion in astrocytes. Gap junctional communication was also found to enable cell-to-cell coordination of actin filaments in astrocytes. This cell-to-cell coordination of actin filaments results in a widely spread intercellular communication by Ca2+ propagation. In conclusion, actin filaments are strongly involved in intracellular and intercellular Ca2+ signaling in astrocytes.
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