title: Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors).
abstract: P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.
authors.affiliation: Department of Pharmacological and Physiological Science, and The Center for Excellence in Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Damien S K
authors.initials: DS
authors.lastname: Samways
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Khakh
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dutertre
authors.forename: Terrance M
authors.initials: TM
authors.lastname: Egan
mesh_terms: D000255:Adenosine Triphosphate; D004058:Diffusion; D006801:Humans; D015640:Ion Channel Gating; D007477:Ions / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D058848:Receptors, Purinergic P2X4 / Q000737:chemistry* / Q000502:physiology*
chemical_list: D007477:Ions; C548226:P2RX4 protein, human; D058848:Receptors, Purinergic P2X4; D000255:Adenosine Triphosphate