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 Ca$^{2+}$-permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca$^{2+}$ 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 Ca$^{2+}$ release from intracellular stores through IP$_3$ receptors and store-operated Ca$^{2+}$ entry. These responses were entirely mediated by P2Y$_1$ and P2Y$_2$ receptors. Agonists of P2X receptors did not evoke Ca$^{2+}$ signals, and nor did ATP when Ca$^{2+}$ release from intracellular stores and store-operated $^{}$Ca$^{}$2+ entry were inhibited. We conclude that ATP-evoked Ca$^{2+}$ signals in cultured human foetal astrocytes are entirely mediated by P2Y$_1$ and P2Y$_2$ receptors, with no contribution from P2X receptors.
