Spontaneous and multifaceted ATP release from astrocytes at the scale of hundreds of synapses

Yoshiki Hatashita, Zhaofa Wu, Hirotaka Fujita, Takuma Kumamoto, Jean Livet, Yulong Li, Manabu Tanifuji, Takafumi Inoue*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Astrocytes participate in information processing by releasing neuroactive substances termed gliotransmitters, including ATP. Individual astrocytes come into contact with thousands of synapses with their ramified structure, but the spatiotemporal dynamics of ATP gliotransmission remains unclear, especially in physiological brain tissue. Using a genetically encoded fluorescent sensor, GRABATP1.0, we discovered that extracellular ATP increased locally and transiently in absence of stimuli in neuron–glia co-cultures, cortical slices, and the anesthetized mouse brain. Spontaneous ATP release events were tetrodotoxin-insensitive but suppressed by gliotoxin, fluorocitrate, and typically spread over 50–250 μm2 area at concentrations capable of activating purinergic receptors. Besides, most ATP events did not coincide with Ca2+ transients, and intracellular Ca2+ buffering with BAPTA-AM did not affect ATP event frequency. Clustering analysis revealed that these events followed multiple distinct kinetics, and blockade of exocytosis only decreased a minor group of slow events. Overall, astrocytes spontaneously release ATP through multiple mechanisms, mainly in non-vesicular and Ca2+-independent manners, thus potentially regulating hundreds of synapses all together.

Original languageEnglish
Pages (from-to)2250-2265
Number of pages16
JournalGLIA
Volume71
Issue number9
DOIs
Publication statusPublished - 2023 Sept

Keywords

  • astrocytes
  • calcium imaging
  • channel-mediated ATP release
  • exocytosis
  • extracellular ATP imaging
  • gliotransmission
  • neuron–glia interactions

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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