Role of purinergic receptor P2Y1 in spatiotemporal Ca2+ dynamics in astrocytes

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

Research output: Contribution to journalArticle

12 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 Ca2+signals. Astrocytes display numerous spontaneous microdomain Ca2+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 Ca2+ signals, we engineered mice (both sexes) to specifically overexpress P2Y1Rs in astrocytes, and we visualized Ca2+ signals via a genetically encoded Ca2+ indicator, GCaMP6f, in astrocytes from adult mice. Astrocytes overexpressing P2Y1Rs showed significantly larger Ca2+ 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 Ca2+signals. Instead, Ca2+waves appeared and propagated to occupy areas that were up to 80-fold larger than microdomain Ca2+ signals. These Ca2+ waves accounted for only 2% of total Ca2+ events, but they were 1.9-fold larger and 2.9-fold longer in duration than microdomain Ca2+ signals at processes. Ca2+ 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 Ca2+ 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

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

ASJC Scopus subject areas

  • Neuroscience(all)

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