P2RX7

P2X7, or P2X purinergic receptor 7, is a member of the P2X receptor family of ligand-gated ion channels. It is encoded by the P2RX7 gene in humans. The receptor is activated by high concentrations of extracellular ATP and functions primarily as a non-selective cation channel. Distinct from other P2X receptors, P2X7 can form a large permeability pore upon prolonged or strong stimulation, allowing passage of large organic ions and dyes, and contributing to cell death.

Upon ATP binding, P2X7 opens to permit Na+ and Ca2+ influx and K+ efflux. Sustained activation can lead to assembly of the NLRP3 inflammasome in various immune cells, caspase-1 activation, and release of pro-inflammatory cytokines such as interleukin-1β and interleukin-18. This signaling axis links P2X7 to inflammatory and immune responses, neuroinflammation, microglial activation, and tissue-damage responses. P2X7 is widely expressed in macrophages, dendritic cells, microglia, and to a lesser extent in neurons and epithelial cells, with expression patterns that vary by tissue and activation state.

Pharmacologically, the receptor is activated by ATP and the potent agonist BzATP, and inhibited by several antagonists including Brilliant Blue G and oxidized ATP, among others, with selective compounds used in research. Genetic variation in P2RX7 includes multiple polymorphisms that can alter receptor function and pore formation, influencing susceptibility to inflammatory and autoimmune conditions in some populations.

In research, P2X7 is investigated as a therapeutic target for inflammatory and neurodegenerative diseases, pain, and graft rejection, with various inhibitors in preclinical and clinical development.