P2X6

P2X6 is a member of the P2X receptor family, a group of ATP-gated nonselective cation channels. It is encoded by the P2RX6 gene and participates in ATP-activated signaling in various tissues. P2X receptors form trimeric channels, with each subunit contributing two transmembrane helices, a large extracellular loop containing ATP-binding sites, and cytoplasmic N- and C-termini. The P2X6 subunit can assemble with other P2X subunits to form functional receptors.

In many experimental systems, homomeric P2X6 channels do not form functional receptors, whereas heteromeric assemblies such as P2X2/6 or P2X4/6 produce functional receptors with distinct biophysical and pharmacological properties. The exact properties of P2X6-containing receptors—such as ATP sensitivity, kinetics, and ion permeability—depend on the subunit composition and cellular context. Activation by extracellular ATP leads to cation influx, notably Na+ and Ca2+, contributing to depolarization and downstream signaling. Modulation by extracellular divalent cations and Mg2+ can also influence channel behavior.

Expression data indicate P2RX6 transcripts are detected in various tissues, including components of the nervous system, though protein-level distribution and functional relevance can vary by species and developmental stage. The physiological roles of P2X6-containing receptors are not fully defined but are implicated in ATP-mediated signaling in neurons and possibly in peripheral tissues, contributing to synaptic transmission and nociceptive processing in certain contexts.

Overall, P2X6 is best understood as a subunit that modulates receptor function through heteromeric assembly, rather than as a functional homomeric channel in many physiological settings.