ATP evokes Ca2+ signals in cultured foetal human cortical astrocytes entirely through G protein-coupled P2Y receptors
Publication Date
2017-08-02Journal Title
Journal of Neurochemistry
ISSN
0022-3042
Publisher
Wiley
Language
English
Type
Article
This Version
VoR
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Taylor, C., & Muller, M. (2017). ATP evokes Ca2+ signals in cultured foetal human cortical astrocytes entirely through G protein-coupled P2Y receptors. Journal of Neurochemistry https://doi.org/10.1111/jnc.14119
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 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.
Keywords
P2X receptor, P2Y1 receptor, P2Y2 receptor, phospholipase C, purinoceptor, store-operated Ca2+ entry
Sponsorship
This work was supported by the Wellcome Trust (101844) and a European Union Horizon 2020 Marie Sklodowska-Curie Individual European Fellowship to M.S.M. (658386).
Funder references
European Commission (658386)
Wellcome Trust (101844/Z/13/Z)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1111/jnc.14119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/265247
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International