Intracellular calcium oscillations induced by ATP in airway epithelial cells

John H. Evans, University of Massachusetts Medical School
Michael J. Sanderson, University of Massachusetts Medical School

Document Type Article


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