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Imaging P2X4 receptor lateral mobility in microglia: regulation by calcium and p38 MAPK

Estelle Toulme1, Baljit S Khakh

  • 1Department of Physiology, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.

The Journal of Biological Chemistry
|March 7, 2012
PubMed

Insights

P2X4 receptors, crucial for neuropathic pain, are dynamically regulated mobile ATP sensors. Their mobility in microglia increases with ATP, calcium, and in activated states, highlighting their role in nervous system dysfunction.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • ATP-gated ionotropic P2X4 receptors are upregulated in activated microglia.
  • These receptors are critical for neuropathic pain development, a microglia-associated disorder.
  • Regulation of plasma membrane P2X4 receptors in microglia is not fully understood.

Purpose of the Study:

  • To investigate the mobility and regulation of P2X4 receptors in the plasma membrane of resting and activated microglia.
  • To understand how P2X4 receptor lateral mobility is influenced by ATP, calcium, and the p38 MAPK pathway.

Main Methods:

  • Single-molecule imaging using quantum dot-labeled P2X4 receptors.
  • Tracking receptor mobility in the processes of resting and activated microglia.

Main Results:

  • Plasma membrane P2X4 receptor lateral mobility in resting microglia is largely random, with mobile and slowly mobile populations.
  • Mobility is P2X subunit- and cell-specific.
  • Lateral mobility increases in an ATP and calcium-dependent manner.
  • The p38 MAPK pathway enhances mobility in activated microglia by regulating slowly mobile receptors.

Conclusions:

  • P2X4 receptors function as dynamically regulated mobile ATP sensors.
  • Receptor mobility increases in response to ATP and during microglial activation.
  • These findings provide insights into the role of P2X4 receptor dynamics in microglia-associated nervous system dysfunction.

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