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

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

研究成果: Article査読

25 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1383-1395
ページ数13
ジャーナルJournal of Neuroscience
38
6
DOI
出版ステータスPublished - 2018 2月 7

ASJC Scopus subject areas

  • 神経科学(全般)

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