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

ABSTRACT: 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 (P2X₄ , P2X₅ , P2X₆ ) and G protein-coupled P2Y receptors (P2Y₁ , P2Y₂ , P2Y₆ , P2Y₁₁ ). In these astrocytes, ATP stimulated Ca²⁺ release from intracellular stores through IP₃ receptors and store-operated Ca²⁺ entry. These responses were entirely mediated by P2Y₁ and P2Y₂ 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 ATP-evoked Ca²⁺ signals in cultured human foetal astrocytes are entirely mediated by P2Y₁ and P2Y₂ receptors, with no contribution from P2X receptors.

SUBMITTER: Muller MS 

PROVIDER: S-EPMC5601250 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature