ATP evokes Ca2+ signals in cultured foetal human cortical astrocytes entirely through protien-coupled P2Y receptors

Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. In rodents, ATP stimulates opening of Ca2+-permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca2+ signals in human astrocytes. Here, we directly assess this hypothesis. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X(4), P2X(5), P2X(6)) and G protein-coupled P2Y receptors (P2Y(1), P2Y(2), P2Y(6), P2Y(11)). In these astrocytes, ATP stimulated Ca2+ release from intracellular stores through IP3 receptors and store-operated Ca2+ entry. These responses were entirely mediated by P2Y(1) and P2Y(2) receptors. Agonists of P2X receptors did not evoke Ca2+ signals, and nor did ATP when Ca2+ release from intracellular stores and store-operated Ca2+ entry were inhibited. We conclude that ATPevoked Ca2+ signals in cultured human foetal astrocytes are entirely mediated by P2Y(1) and P2Y(2) receptors, with no contribution from P2X receptors.