Stimulation of the ionotropic nucleotide receptor P2X₇ with extracellular ATP induces the efflux of K⁺ and the influx of Ca⁺⁺ and Na⁺. Following prolonged receptor stimulation, there is the formation of a nonselective pore that has been reported to involve the pannexins. Upon ligand binding, P2X₇ can initiate multiple signaling events, including the production of reaction oxygen species, the activation of multiple MAP kinase (MAPK) cascades, and the expression/activation of numerous transcription factors (shown in green). The role of the various P2X ₇-initiated signaling cascades in the activation of these transcription factors is still poorly understood, but many reports support a central role for intracellular Ca⁺⁺ fluxes and MAPK signaling cascades. For example, Ca⁺⁺ fluxes appear linked to the nuclear translocation of the NFAT, whereas reactive oxygen species production and Ca⁺⁺ fluxes have been linked to NF-κB nuclear translocation, and MAPK-dependent events appear essential for the activation of the CREB and Egr transcription factors. In addition, the transcriptional regulation and expression of only a small number of P2X₇-dependent genes has been elucidated to date, including the P2X₇-mediated expression of several Egr and AP-1 (cFos, FosB, JunB) transcription factors. Pannexins: family of transmembrane channels; important in P2X₇-mediated IL-1β processing and release. I-κB: NF-κB regulatory protein that is degraded after phosphorylation, allowing NF-κB translocation into the nucleus. p50/p65: NF-κB subunits proposed to be P2X₇ agonist-induced. Elk-1 (Ets LiKe gene-1): Ets transcription factor of the ternary complex factor subfamily that binds to the serum response element in the promoter of genes; linked to the expression of Egr1 after P2X₇ activation. CBP (CREB-binding protein): required for CREB-mediated gene expression; P2X₇ agonists induce CREB/CBP complex formation. P: phospho-group; regulates the activation of various proteins. Jun (JunB, cJun): members of the AP-1 family of transcription factors; JunB and cJun expression is upregulated after P2X₇ stimulation

Human P2X₇ possesses a predicted extracellular ATP binding domain, two transmembrane domains (TM), an intracellular trafficking domain, and a lipid binding domain (LBD). In addition, numerous P2X₇ SNPs have been identified, including several with reduced function. Non-synonymous SNPs that exhibit reduced activity are represented in brown, and SNPs that have been correlated with human disease are shown in blue