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PMID: 18587390 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Gating the pore of P2X receptor channels.

Nature neuroscience ·Vol. 11 ·No. 8 ·2008-08-00 ·Pages 883-7

Li M, Chang TH, Silberberg SD, Swartz KJ

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.

MeSH Terms
Amino Acid Substitution/genetics Animals Cadmium Compounds/pharmacology Cell Line Cell Membrane/metabolism Cysteine/genetics,metabolism Humans Ion Channel Gating/drug effects,genetics,physiology Kidney/cytology,drug effects,metabolism Mesylates/pharmacology Models, Biological Mutagenesis, Site-Directed Patch-Clamp Techniques Protein Structure, Tertiary/genetics,physiology Rats Receptors, Purinergic P2/drug effects,genetics,metabolism Receptors, Purinergic P2X2 Silver Nitrate/pharmacology Transfection
Chemicals
Cadmium Compounds Mesylates P2RX2 protein, human Receptors, Purinergic P2 Receptors, Purinergic P2X2 (2-(trimethylammonium)ethyl)methanethiosulfonate Silver Nitrate Cysteine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Li Mufeng
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.
Chang Tsg-Hui
Silberberg Shai D
Swartz Kenton J
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Article Info
Journal
Nature neuroscience
Abbr.
Nat Neurosci
ISSN
1546-1726
DOI
10.1038/nn.2151
Published
2008-08-00
Epub
2008-00-29
Pages
883-7
Language
English
Region
United States
NLM ID
9809671
PMCID
PMC2629452
Subset
IM
Grants
Intramural NIH HHS · ZIA NS003018-03 · United States
External Links
PubMed source DOI: 10.1038/nn.2151 PMC Full Text View journal details
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