Ion Access Pathway to the Transmembrane Pore in P2X Receptors

Abstract

P2X receptors are ATP-gated channels that mediate cation influx to evoke action potentials or trigger intracellular signaling, important in sensory signal transmission and inflammatory responses. However, the molecular mechanism of how cations penetrate the extracellular region of the receptor and access the transmembrane pore is unknown. Examination of the closed state crystal structure predicts two potential pathways: i) three fenestrations located above the membrane (lateral pathways) and ii) the central void along the molecular three-fold axis of symmetry (central pathway).