Intercellular calcium signaling mediated by point-source burst release of ATP

Calcium signaling, manifested as intercellular waves of rising cytosolic calcium, is, in many cell types, the result of calcium-induced secretion of ATP and activation of purinergic receptors. The mechanism by which ATIP is released has hitherto not been established. Here, we show by real-time bioluminescence imaging that ATIP efflux is not uniform across a field of cells but is restricted to brief, abrupt point-source bursts. The ATP bursts emanate from single cells and manifest the transient opening of nonselective membrane channels, which admits fluorescent indicators of less than or equal to1.5 kDa. These observations challenge the existence of regenerative ATIP release, because ATP efflux is finite and restricted to a point source. Transient efflux of cytosolic nucleotides from a subset of cells may represent a conserved pathway for coordinating local activity of electrically nonexcitable cells, because identical patterns of ATIP release were identified in human astrocytes, endothelial cells, and bronchial epithelial cells.