Gating the pore of P2X receptor channels

Nat Neurosci. 2008 Aug;11(8):883-7. doi: 10.1038/nn.2151. Epub 2008 Jun 29.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Substitution / genetics
  • Animals
  • Cadmium Compounds / pharmacology
  • Cell Line
  • Cell Membrane / metabolism
  • Cysteine / genetics
  • Cysteine / metabolism
  • Humans
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / genetics*
  • Ion Channel Gating / physiology*
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism
  • Mesylates / pharmacology
  • Models, Biological
  • Mutagenesis, Site-Directed
  • Patch-Clamp Techniques
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Rats
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X2
  • Silver Nitrate / pharmacology
  • Transfection


  • Cadmium Compounds
  • Mesylates
  • P2RX2 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X2
  • (2-(trimethylammonium)ethyl)methanethiosulfonate
  • Silver Nitrate
  • Cysteine