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Updated: May 9, 2026
Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
Microglia release ATP by exocytosis
Yoshio Imura1, Yosuke Morizawa, Ryohei Komatsu
1Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato, Chuo, Yamanashi, Japan.
Abstract:
Microglia survey the brain environment by sensing several types of diffusible molecules, among which extracellular nucleotides released/leaked from damaged cells have central roles. Microglia sense ATP or other nucleotides by multiple P2 receptors, after which they change into several different phenotypes. However, so far, it is largely unknown whether microglia themselves release ATP and, if so, by what mechanism. Here we show that exocytosis is the mechanism by which microglia release ATP. When we stimulated microglia with ionomycin, they released ATP and the release was dependent on Ca²⁺, vesicular H⁺-ATPase, or SNAREs but independent of connexin/pannexin hemichannels. VNUT was found to be expressed in microglia and exhibited no colocalization with lysosome. We also visualized the exocytosis of ATP by a quinacrine-based fluorescent time-lapse imaging. Moreover, we found that lipopolysaccharide increased the ionomycin-induced release of ATP, which was dependent on the increase in VNUT. Taken together, our data suggested that exocytosis is the mechanism of ATP release from microglia. When activated, they would release ATP by increasing VNUT-dependent exocytotic mechanisms.
Insights
Microglia release adenosine triphosphate (ATP) via exocytosis, a process involving calcium, vesicular H⁺-ATPase, and SNAREs. This ATP release mechanism is crucial for activated microglia function.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia, the brain's immune cells, sense extracellular nucleotides like ATP to modulate their function.
- The mechanism by which microglia release ATP remains largely uncharacterized.
Purpose of the Study:
- To elucidate the mechanism of ATP release from microglia.
- To investigate the role of exocytosis in microglial ATP release.
Main Methods:
- Microglial stimulation with ionomycin to induce ATP release.
- Assessment of ATP release dependence on Ca²⁺, vesicular H⁺-ATPase, SNAREs, and hemichannels.
- Analysis of Vesicular Nucleotide Transporter (VNUT) expression and localization.
- Fluorescent time-lapse imaging of ATP exocytosis using quinacrine.
- Investigating the effect of lipopolysaccharide (LPS) on ATP release.
Main Results:
- Microglia release ATP through a Ca²⁺-dependent exocytotic process.
- ATP release was dependent on vesicular H⁺-ATPase and SNAREs, but not connexin/pannexin hemichannels.
- VNUT is expressed in microglia and its expression increases upon LPS stimulation, correlating with enhanced ATP release.
- Exocytosis of ATP by microglia was directly visualized using time-lapse imaging.
Conclusions:
- Exocytosis is the primary mechanism for ATP release from microglia.
- VNUT-dependent exocytosis is upregulated in activated microglia, contributing to extracellular ATP signaling.
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