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 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.
Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. John.Evans@ummed.edu
J H
JH
Evans
M J
MJ
Sanderson
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009991:Oscillometry; D011817:Rabbits; D014018:Tissue Distribution / Q000502:physiology; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology
D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium; D014544:Uridine Triphosphate