Intracellular calcium oscillations induced by ATP in airway epithelial cells

In airway epithelial cells, extracellular ATP (ATP(o)) stimulates an initial transient increase in intracellular Ca2+ concentration that is followed by periodic increases in intracellular Ca2+ concentration (Ca2+ oscillations). The characteristics and mechanism of these ATP-induced Ca2+ responses were studied in primary cultures of rabbit tracheal cells with digital video fluorescence microscopy and the Ca2+-indicator dye fura 2. The continual presence of ATP(o) at concentrations of 0.1-100 mu M stimulated Ca2+ oscillations that persisted for 20 min. The frequency of the Ca2+ oscillations was found to be dependent on both ATP(o) concentration and intrinsic sensitivity of each cell to ATP(o). Cells exhibited similar Ca2+ oscillations to extracellular UTP (UTPo), but the oscillations typically occurred at lower UTPo concentrations. The ATP-induced Ca2+ oscillations were abolished by the phospholipase C inhibitor U-73122 and by the endoplasmic reticulum Ca2+-pump inhibitor thapsigargin but were maintained in Ca2+-free medium. These results are consistent with the hypothesis that in airway epithelial cells ATP(o) and UTPo act via P2U purinoceptors to stimulate Ca2+ oscillations by the continuous production of inositol 1,4,5-trisphosphate and the oscillatory release of Ca2+ from internal stores. ATP-induced Ca2+ oscillations of adjacent individual cells occurred independently of each other. By contrast, a mechanically induced intercellular Ca2(+) wave propagated through a field of Ca2+-oscillating cells. Thus Ca2+ oscillations and propagating Ca2+ waves are two fundamental modes of Ca2+ signaling that exist and operate simultaneously in airway epithelial cells.