Gating the pore of P2X receptor channels

Mufeng Li, Tsg Hui Chang, Shai D. Silberberg, Kenton J. Swartz

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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.

Original languageEnglish
Pages (from-to)883-887
Number of pages5
JournalNature Neuroscience
Volume11
Issue number8
DOIs
StatePublished - 1 Aug 2008
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience (all)

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