Intercellular calcium waves mediated by inositol trisphosphate

Abstract

Intercellular calcium waves occur in diverse cells. Those that are induced by mechanical stimulation have been extensively investigated in epithelial and glial cells. Mechanical stimulation of an individual cell initiates an increase in the intracellular free calcium concentration, [Ca2+]i, that spreads across the cell. At the cell border this intracellular Ca2+ wave is arrested but, after a brief delay, similar Ca2+ waves occur in adjacent cells. The repetition of this process results in the propagation of an intercellular Ca2+ wave through a limited number of cells. The propagation of intercellular Ca2+ waves correlates with the presence of functional gap junctions and occurs in the absence of extracellular Ca2+ or following the microinjection of inositol 1,4,5-trisphosphate (InsP3). The propagation of intercellular Ca2+ waves is inhibited by heparin (an InsP3 receptor antagonist) and by U73122 (a phospholipase C inhibitor) or when intracellular Ca2+ stores are depleted with thapsigargin. These characteristics suggest that mechanical stimulation initiates InsP3 production and that intercellular Ca2+ waves are propagated through the movement of InsP3 through gap junctions. Mathematical modelling supports the idea that diffusion of InsP3 is a viable hypothesis for the generation of intercellular Ca2+ waves. The ability of cells to display changes in [Ca2+]i that are independent of neighbouring cells (i.e., asynchronous Ca2+ oscillations) and the low diffusion constant of Ca2+ suggest that Ca2+ itself is not a major messenger moving between cells to propagate Ca2+ waves.