title: Vesicular ATP is the predominant cause of intercellular calcium waves in astrocytes.
abstract: Brain astrocytes signal to each other and neurons. They use changes in their intracellular calcium levels to trigger release of transmitters into the extracellular space. These can then activate receptors on other nearby astrocytes and trigger a propagated calcium wave that can travel several hundred micrometers over a timescale of seconds. A role for endogenous ATP in calcium wave propagation in hippocampal astrocytes has been suggested, but the mechanisms remain incompletely understood. Here we explored how calcium waves arise and directly tested whether endogenously released ATP contributes to astrocyte calcium wave propagation in hippocampal astrocytes. We find that vesicular ATP is the major, if not the sole, determinant of astrocyte calcium wave propagation over distances between approximately 100 and 250 microm, and approximately 15 s from the point of wave initiation. These actions of ATP are mediated by P2Y1 receptors. In contrast, metabotropic glutamate receptors and gap junctions do not contribute significantly to calcium wave propagation. Our data suggest that endogenous extracellular astrocytic ATP can signal over broad spatiotemporal scales.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.
authors.forename: David N
authors.initials: DN
authors.lastname: Bowser
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Khakh
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000814:Aniline Compounds; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D020126:Brefeldin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism*; D004058:Diffusion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D018942:Macrolides; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D014966:Xanthenes; C057620:bafilomycin A; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D020126:Brefeldin A; C059715:Fluo-3; D011732:Pyridoxal Phosphate; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001081:Apyrase; D006180:Proton-Translocating ATPases; D002118:Calcium