P2X7

P2X7 is a member of the P2X purinergic receptor family. It is a ligand-gated ion channel that is activated by extracellular ATP. Unlike many other P2X receptors, P2X7 requires relatively high ATP concentrations for activation, and prolonged stimulation can convert the channel into a large, non-selective pore that allows passage of large organic cations and dyes up to roughly 900 Da, which can contribute to cell death through necrosis or pyroptosis.

The receptor forms a trimer and has a distinctive long intracellular C-terminus that participates in signaling and pore formation. Upon activation, P2X7 mediates rapid Na+ and Ca2+ influx and K+ efflux, followed by functional changes that are influenced by the cellular context and accessory proteins. This signaling can interact with cytoskeletal elements and vesicular trafficking pathways, linking P2X7 to various cellular responses.

Expression of P2X7 is highest in the immune system, including macrophages, microglia, and dendritic cells, where it plays a key role in inflammatory signaling. It is also found in other tissues, with expression patterns that can vary by species, cell type, and inflammatory state. In the brain, microglia express P2X7 and participate in neuroinflammatory responses; expression in neurons and astrocytes is less consistent across studies.

Physiological and pathological roles of P2X7 include activation of the NLRP3 inflammasome, caspase-1 activation, and the release of interleukin-1β and interleukin-18. This receptor is implicated in innate immune responses, chronic pain, neurodegenerative conditions, bone remodeling, and cancer-related inflammation. Pharmacologically, BzATP is a potent agonist, while several antagonists such as brilliant blue G and others are used in research to dissect P2X7 function; translation into clinically approved modulators remains an ongoing area of investigation.