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Updated: Jul 26, 2026

Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
Published on: August 15, 2012
Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human
Manju Tewari1, Stephanie Michalski1, Terrance M Egan1
1Department of Pharmacology and Physiology, and The Henry and Amelia Nasrallah Institute for Translational Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Abstract:
P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in a variety of cells. Five of the family members are sensitive to low concentrations of extracellular ATP, while the P2X6 receptor has an unknown affinity. The last subtype, the P2X7 receptor, is unique in requiring millimolar concentrations to fully activate in humans. This low sensitivity imparts the agonist with the ability to act as a damage-associated molecular pattern that triggers the innate immune response in response to the elevated levels of extracellular ATP that accompany inflammation and tissue damage. In this review, we focus on microglia because they are the primary immune cells of the central nervous system, and they activate in response to ATP or its synthetic analog, BzATP. We start by introducing purinergic receptors and then briefly consider the roles that microglia play in neurodevelopment and disease by referencing both original works and relevant reviews. Next, we move to the role of extracellular ATP and P2X receptors in initiating and/or modulating innate immunity in the central nervous system. While most of the data that we review involve work on mice and rats, we highlight human studies of P2X7R whenever possible.
Insights
P2X receptors, particularly P2X7, are key in innate immunity. Microglia, the brain
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- P2X receptors are ATP-gated ion channels involved in cellular responses.
- P2X7 receptors require high ATP concentrations and act as damage-associated molecular patterns.
- Microglia are the primary immune cells in the central nervous system.
Purpose of the Study:
- To review the role of extracellular ATP and P2X receptors in central nervous system innate immunity.
- To focus on microglia activation by ATP and its analogs.
- To highlight human studies of P2X7R where possible.
Main Methods:
- Literature review of original works and relevant reviews.
- Focus on studies involving microglia activation by ATP and BzATP.
- Emphasis on P2X7 receptor function in innate immunity.
Main Results:
- Extracellular ATP and P2X receptors initiate and modulate innate immune responses in the CNS.
- Microglia activation by ATP is central to neuroinflammation.
- P2X7 receptor's role in immune signaling is significant, especially in response to tissue damage.
Conclusions:
- P2X receptors, particularly P2X7, are critical mediators of innate immunity in the CNS.
- Microglia play a pivotal role in ATP-mediated neuroinflammation.
- Understanding P2X7R function is crucial for developing therapies for neurological disorders.
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