title: Differential properties of astrocyte calcium waves mediated by P2Y1 and P2Y2 receptors.
abstract: Intercellular spread of Ca2+ waves is the primary manifestation of cell-to-cell communication among astrocytes. Ca2+ waves propagate via the release of a diffusible extracellular messenger that has been identified as ATP. In dorsal spinal astrocytes, Ca2+ waves are mediated by activation of two functionally distinct subtypes of metabotropic purinoceptor: the P2Y1 receptor and a receptor previously classified as P2U. Here, we show that the P2U receptor is molecularly and pharmacologically identical to the cloned P2Y2 receptor. Both P2Y1 and P2Y2 receptors are necessary for full Ca2+ wave propagation in spinal astrocytes. Conversely, heterologous expression of either P2Y1 or P2Y2 receptors is sufficient for Ca2+ waves, and expressing these receptor subtypes together recapitulates the characteristics of Ca2+ waves in spinal astrocytes. Thus, P2Y1 and P2Y2 receptors are both necessary and sufficient for propagation of Ca2+ waves. Furthermore, we demonstrate that there are dramatic differences in the characteristics of Ca2+ waves propagating through each receptor subtype: Ca2+ waves propagating via P2Y2 receptors travel faster and further than those propagating via P2Y1 receptors. We find that the nucleotidase apyrase selectively blocks Ca2+ wave propagation through P2Y2 receptors but accelerates Ca2+ waves propagating through P2Y1 receptors. Taking our results together with those from the literature, we suggest that mediation of Ca2+ waves by ATP leading to activation of two subtypes of receptor, P2Y1 and P2Y2, may be a general principle for gliotransmission in the CNS. Thus, processes that alter expression or function of these receptors may control the rate and extent of astrocyte Ca2+ waves.
authors.affiliation: Programme in Brain and Behaviour, Hospital For Sick Children, University of Toronto, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Conor J
authors.initials: CJ
authors.lastname: Gallagher
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010812:Physical Stimulation; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology; D013498:Suramin / Q000494:pharmacology; D014162:Transfection; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: C092431:6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP; D004791:Enzyme Inhibitors; C546382:P2RY1 protein, human; C546385:P2RY2 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D058473:Receptors, Purinergic P2Y2; C104749:purinoceptor P2Y4; C099845:purinoceptor P2Y6; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; D001081:Apyrase; D002118:Calcium; D014544:Uridine Triphosphate