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Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury

Stuart E Samuels1, Jeffrey B Lipitz, Gerhard Dahl

  • 1Neuroscience Program, University of Miami School of Medicine, Miami, FL 33136, USA. SSamuels@med.miami.edu

The Journal of General Physiology
|September 30, 2010
PubMed

Insights

Glial cells release adenosine triphosphate (ATP) through innexin channels, which is crucial for guiding microglia immune cells to injury sites in the central nervous system.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia are central nervous system immune cells that migrate to injury sites.
  • Adenosine triphosphate (ATP) release by injured glial cells is a known activator of microglia.
  • The precise mechanism of ATP release from glial cells remains incompletely understood.

Purpose of the Study:

  • To investigate the role of glial cell membrane channels in ATP release.
  • To determine the necessity of ATP release from glia for microglial migration to nerve injury sites.

Main Methods:

  • Utilized a leech model with giant glial cells ensheathing nerve connectives.
  • Administered apyrase to hydrolyze ATP and carbenoxolone (CBX) to block innexons.
  • Performed RNA interference (RNAi) targeting innexin1 and innexin2.
  • Measured ATP release, calcium waves, and microglial migration and accumulation.

Main Results:

  • Blocking innexons with CBX or hydrolyzing ATP with apyrase reduced microglial movement and accumulation at lesions.
  • Restoration of ATP in CBX-treated leeches recovered microglial migration.
  • Innexin2 (Hminx2) RNAi inhibited ATP release and microglial migration, while innexin1 (Hminx1) RNAi did not.
  • Glial calcium waves and intracellular calcium responses were independent of ATP release.

Conclusions:

  • Innexin channels in glial cells are essential for releasing ATP.
  • Glial ATP release via innexin channels is required for microglial migration and accumulation following nerve injury.
  • ATP acts as a key signaling molecule mediating microglial response to nerve damage.

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