Role of purinergic receptor P2Y1 in spatiotemporal Ca 2+ dynamics in astrocytes

Eiji Shigetomi, Yukiho J. Hirayama, Kazuhiro Ikenaka, Kenji F. Tanaka, Schuichi Koizumi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Fine processes of astrocytes enwrap synapses and are well positioned to sense neuronal information via synaptic transmission. In rodents, astrocyte processes sense synaptic transmission via Gq-protein coupled receptors (GqPCR), including the P2Y1 receptor (P2Y1R), to generate Ca 2+ signals. Astrocytes display numerous spontaneous microdomain Ca 2+ signals; however, it is not clear whether such signals are due to local synaptic transmission and/or in what timeframe astrocytes sense local synaptic transmission. To ask whether GqPCRs mediate microdomain Ca 2+ signals, we engineered mice (both sexes) to specifically overexpress P2Y1Rs in astrocytes, and we visualized Ca 2+ signals via a genetically encoded Ca 2+ indicator, GCaMP6f, in astrocytes from adult mice. Astrocytes overexpressing P2Y1Rs showed significantly larger Ca 2+ signals in response to exogenously applied ligand and to repetitive electrical stimulation of axons compared with controls. However, we found no evidence of increased microdomain Ca 2+ signals. Instead, Ca 2+ waves appeared and propagated to occupy areas that were up to 80-fold larger than microdomain Ca 2+ signals. These Ca 2+ waves accounted for only 2% of total Ca 2+ events, but they were 1.9-fold larger and 2.9-fold longer in duration than microdomain Ca 2+ signals at processes. Ca 2+ waves did not require action potentials for their generation and occurred in a probenecid-sensitive manner, indicating that the endogenous ligand for P2Y1R is elevated independently of synaptic transmission. Our data suggest that spontaneous microdomain Ca 2+ signals occur independently of P2Y1R activation and that astrocytes may not encode neuronal information in response to synaptic transmission at a point source of neurotransmitter release.

Original languageEnglish
Pages (from-to)1383-1395
Number of pages13
JournalJournal of Neuroscience
Volume38
Issue number6
DOIs
Publication statusPublished - 2018 Feb 7

Keywords

  • ATP
  • Astrocyte
  • Astrocyte process
  • Calcium
  • GECI
  • P2Y1 receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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