Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes

Sylvia O. Suadicani, Rodolfo Iglesias, David C. Spray, Eliana Scemes

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R-Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinasebinding site) of the C-terminus of the P2X 7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membranepermeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

Original languageEnglish (US)
Article numbere00005
Pages (from-to)55-63
Number of pages9
JournalASN Neuro
Volume1
Issue number1
DOIs
Publication statusPublished - 2009

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Keywords

  • ATP release
  • Gap junction
  • Glia
  • Hemichannel
  • Pannexin
  • Purinergic receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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