P2X4 Receptor

P2X4 receptor is an extracellular ATP-gated trimeric cation channel that supports Ca²⁺-linked purinergic signaling^[1]. Mechanistically, P2X4 activation in spinal microglia promotes BDNF release and NR1 phosphorylation, linking receptor upregulation after peripheral nerve injury to neuropathic pain models^[2]. In nerve-injury models, induced spinal microglial P2X4 is necessary and sufficient for tactile allodynia^[3]. Compared with related P2X7, P2X4 shares ATP-gated cation-channel architecture but shows disputed direct P2X4/P2X7 interaction in native systems, so isoform-selective validation remains essential^[4]. For experimental applications, ivermectin acts as a positive allosteric modulator of human P2X4, while NP-1815-PX, BX430, and BAY-1797 support antagonist-based interrogation of P2X4 function^[5][6][7].- P2X4 links extracellular ATP sensing to Ca²⁺ signaling in purinergic receptor biology.- Microglial P2X4 supports neuropathic pain modeling through BDNF-associated spinal signaling.- Selective antagonists help separate P2X4 mechanisms from related P2X receptor isoforms.