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

7 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

Fingerprint

Purinergic P2Y1 Receptors
Astrocytes
Synaptic Transmission
Gq-G11 GTP-Binding Protein alpha Subunits
Ligands
Probenecid
Synapses
Electric Stimulation
Action Potentials
Neurotransmitter Agents
Axons
Rodentia

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of purinergic receptor P2Y1 in spatiotemporal Ca2+ dynamics in astrocytes. / Shigetomi, Eiji; Hirayama, Yukiho J.; Ikenaka, Kazuhiro; Tanaka, Kenji; Koizumi, Schuichi.

In: Journal of Neuroscience, Vol. 38, No. 6, 07.02.2018, p. 1383-1395.

Research output: Contribution to journalArticle

Shigetomi, Eiji ; Hirayama, Yukiho J. ; Ikenaka, Kazuhiro ; Tanaka, Kenji ; Koizumi, Schuichi. / Role of purinergic receptor P2Y1 in spatiotemporal Ca2+ dynamics in astrocytes. In: Journal of Neuroscience. 2018 ; Vol. 38, No. 6. pp. 1383-1395.
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