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Updated: Jul 16, 2026

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
07:27

Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices

Published on: January 31, 2019

ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium

Long-Jun Wu1, Kunjumon I Vadakkan, Min Zhuo

  • 1Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Glia
|March 16, 2007
PubMed

Insights

Adenosine triphosphate (ATP) triggers microglial cell movement towards brain injuries via P2Y receptors. This process involves specific potassium channels and the phosphoinositide 3-kinase pathway, crucial for microglial response.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglial cells, the brain's resident macrophages, play a vital role in responding to injuries and infections.
  • Previous research indicated that adenosine triphosphate (ATP) and P2Y receptors mediate microglial chemotaxis to local brain injury.
  • The precise molecular mechanisms underlying ATP-driven microglial chemotaxis remained largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms responsible for adenosine triphosphate (ATP)-induced microglial chemotaxis.
  • To investigate the role of P2Y receptors and associated ion channels in microglial motility.
  • To determine the signaling pathways involved in ATP-mediated microglial responses.

Main Methods:

  • Utilized simultaneous perforated whole-cell recordings and time-lapse confocal imaging in GFP-labeled microglia.
  • Employed acute brain slices from adult mice to study microglial behavior in a native environment.
  • Investigated the involvement of specific signaling pathways, including phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK).

Main Results:

  • A strong correlation was observed between ATP-induced microglial chemotaxis and P2Y receptor-associated outward potassium currents.
  • Activation of both P2Y receptors and their associated potassium channels is essential for ATP-induced chemotaxis and basal microglial motility.
  • Microglial chemotaxis in response to ATP necessitates the activation of the phosphoinositide 3-kinase (PI3K) pathway, but not the mitogen-activated protein kinase (MAPK) pathway.

Conclusions:

  • P2Y receptor-associated outward potassium channels are critical components of the molecular machinery driving ATP-induced microglial motility.
  • The phosphoinositide 3-kinase (PI3K) signaling pathway is indispensable for ATP-mediated microglial chemotaxis and movement in the brain.
  • These findings provide significant insights into the mechanisms governing microglial responses to injury signals like ATP.

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