P2Y(1) purinoceptor-mediated Ca2+ signaling and Ca2+ wave propagation in dorsal spinal cord astrocytes

ATP is known to act as an extracellular messenger mediating the propagation of Ca2+ waves in astrocyte networks. ATP mediates Ca2+ waves by activating P2Y purinoceptors, which mobilize intracellular Ca2+ in astrocytes. A numb er of P2Y purinoceptor subtypes have been discovered, but it is not known w hich P2Y subtypes participate in transmitting astrocyte Ca2+ waves. Here, w e show that ATP analogs that are selective agonists for the P2Y(1) subtype of purinoceptor caused release of intracellular Ca2+ in astrocytes from the dorsal spinal cord. The Ca2+ responses were blocked by adenosine-3'-phosph o- 5'-phosphosulfate, an antagonist known to selectively inhibit P2Y(1) but not other P2Y purinoceptor subtypes. Also, we show that P2Y(1) mRNA is exp ressed in dorsal spinal cord astrocytes. Furthermore, expression of P2Y(1) in an astrocytoma cell line lacking endogenous purinoceptors was sufficient to permit propagation of intercellular Ca2+ waves. Finally, Ca2+ wave prop agation in dorsal spinal cord astrocytes was suppressed by pharmacologicall y blocking P2Y(1) purinoceptors. Together, these results indicate that dors al spinal astrocytes express functional P2Y(1) purinoceptors, which partici pate in the transmission of Ca2+ waves. Ca2+ waves in astrocytes have been implicated as a major signaling pathway coordinating glial and neuronal act ivity; therefore, P2Y(1) purinoceptors may represent an important link in c ell-cell signaling in the CNS.