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 ATP is released has hitherto not been established. Here, we show by real-time bioluminescence imaging that ATP 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 < or = 1.5 kDa. These observations challenge the existence of regenerative ATP 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 ATP release were identified in human astrocytes, endothelial cells, and bronchial epithelial cells.
Arcuino
Gregory
G
Department of Cell Biology, Anatomy, and Pathology, New York Medical College, Valhalla, NY 10595, USA.
Lin
Jane H-C
JH
Takano
Takahiro
T
Liu
Collins
C
Jiang
Li
L
Gao
Qun
Q
Kang
Jian
J
Nedergaard
Maiken
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology*; D014471:Umbilical Veins
D000255:Adenosine Triphosphate