title: Gating the pore of P2X receptor channels.
abstract: Three families of ligand-activated ion channels mediate synaptic communication between excitable cells in mammals. For pentameric channels related to nicotinic acetylcholine receptors and tetrameric channels such as glutamate receptors, the pore-forming and gate regions have been studied extensively. In contrast, little is known about the structure of trimeric P2X receptor channels, a family of channels that are activated by ATP and are important in neuronal signaling, pain transmission and inflammation. To identify the pore-forming and gate regions in P2X receptor channels, we introduced cysteine residues throughout the two transmembrane (TM) segments and studied their accessibility to thiol-reactive compounds and ions. Our results show that TM2 lines the central ion-conduction pore, TM1 is positioned peripheral to TM2 and the flow of ions is minimized in the closed state by a gate formed by the external region of TM2.
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, US National Institute of Neurological Disorders and Stroke, US National Institutes of Health, 35 Convent Drive, MSC 3701, Bethesda, Maryland 20892, USA.
authors.forename: Mufeng
authors.initials: M
authors.lastname: Li
authors.forename: Tsg-Hui
authors.initials: TH
authors.lastname: Chang
authors.forename: Shai D
authors.initials: SD
authors.lastname: Silberberg
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D019187:Cadmium Compounds / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008698:Mesylates / Q000494:pharmacology; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2; D012835:Silver Nitrate / Q000494:pharmacology; D014162:Transfection
chemical_list: D019187:Cadmium Compounds; D008698:Mesylates; C546401:P2RX2 protein, human; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; C109154:(2-(trimethylammonium)ethyl)methanethiosulfonate; D012835:Silver Nitrate; D003545:Cysteine