P2X receptors in GtoPdb v.2025.3

Abstract

P2X receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on P2X Receptors [49, 150]) have a trimeric topology [121, 132, 148, 201] with two putative TM domains per P2X subunit, gating primarily Na⁺, K⁺ and Ca²⁺, exceptionally Cl^-. The Nomenclature Subcommittee has recommended that for P2X receptors, structural criteria should be the initial basis for nomenclature where possible. X-ray crystallography indicates that functional P2X receptors are trimeric and three agonist molecules are required to bind to a single trimeric assembly in order to activate it [121, 148, 97, 105, 181]. Native receptors may occur as either homotrimers (e.g. P2X1 in smooth muscle) or heterotrimers (e.g. P2X2:P2X3 in the nodose ganglion [284], P2X1:P2X5 in mouse cortical astrocytes [166], and P2X2:P2X5 in mouse dorsal root ganglion, spinal cord and mid pons [53, 238]. P2X2, P2X4 and P2X7 receptor activation can lead to influx of large cationic molecules, such as NMDG⁺, Yo-Pro, ethidium or propidium iodide [215]. The permeability of the P2X7 receptor is modulated by the amount of cholesterol in the plasma membrane [197]. The hemi-channel pannexin-1 was initially implicated in the action of P2X7 [216], but not P2X2, receptors [41], but this interpretation is probably misleading [219]. Convincing evidence now supports the view that the activated P2X7 receptor is immediately permeable to large cationic molecules, but influx proceeds at a much slower pace than that of the small cations Na⁺, K⁺, and Ca²⁺ [67].