Purinergic receptor P2X4 (P2X4)

The Purinergic receptor P2X4 (P2X4) is a trimeric, ATP-gated nonselective cation channel that belongs to the P2X family of ligand-gated ion channels[1][2][3][5][6]. It is encoded by the *P2RX4* gene in humans. P2X4 is widely expressed in the central and peripheral nervous systems, microglia, endothelial and epithelial cells, glandular tissues, smooth muscle, and various organs such as the bladder, gastrointestinal tract, and heart[1][3][5]. P2X4 is highly permeable to calcium and sodium ions upon activation by extracellular ATP, mediating rapid depolarization and downstream signaling that influences neurotransmitter release, inflammation, nociception (pain transmission), and cellular apoptosis[1][3][5]. Its unique subcellular localization includes the plasma membrane and intracellular compartments, especially lysosomes, where it participates in vesicle fusion and response to pH changes. P2X4 plays critical roles in neuropathic and inflammatory pain, alcohol-induced microglial responses, cardiac function, and several pathologies, making it an emerging therapeutic target. Inhibition or genetic loss of P2X4 function has shown efficacy in preclinical models of pain and neuroinflammation, but its widespread physiological roles require careful consideration for therapeutic development[2][3][4][5].

Other names

P2RX4P2X purinoceptor 4ATP receptorATP-gated cation channel proteinP2X receptor subunit 4purinoceptor P2X4P2X4Rligand-gated ion channel 4P2X4 receptor

Agonists (e.g., ATP) activate the cation channel leading to Ca²⁺ influx and cellular response; antagonists inhibit channel opening and downstream signaling by allosteric or competitive blockade