Pore dilation of neuronal P2X receptor channels

Nat Neurosci. 1999 Apr;2(4):315-21. doi: 10.1038/7225.

Abstract

P2X receptors are ligand-gated ion channels activated by the binding of extracellular adenosine 5'-triphosphate (ATP). Brief (< 1 s) applications of ATP to nodose ganglion neurons or to cells transfected with P2X2 or P2X4 receptor cDNAs induce the opening of a channel selectively permeable to small cations within milliseconds. We now show that, during longer ATP application (10-60 s), the channel also becomes permeable to much larger cations such as N-methyl-D-glucamine and the propidium analog YO-PRO-1. This effect is enhanced in P2X2 receptors carrying point mutations in the second transmembrane segment. Progressive dilation of the ion-conducting pathway during prolonged activation reveals a mechanism by which ionotropic receptors may alter neuronal function.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Amino Acid Substitution
  • Animals
  • Benzoxazoles
  • Cell Line
  • Cell Membrane Permeability
  • DNA, Complementary / genetics
  • Fluorescent Dyes / metabolism
  • Humans
  • Ion Transport
  • Meglumine / metabolism
  • Mice
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nodose Ganglion / cytology
  • Patch-Clamp Techniques
  • Point Mutation
  • Quinolinium Compounds
  • Rats
  • Receptors, Purinergic P2 / chemistry*
  • Receptors, Purinergic P2 / genetics
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2 / physiology
  • Receptors, Purinergic P2X2
  • Receptors, Purinergic P2X4
  • Receptors, Purinergic P2X7
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology
  • Receptors, Serotonin, 5-HT3
  • Second Messenger Systems
  • Serotonin / pharmacology
  • Transfection

Substances

  • Benzoxazoles
  • DNA, Complementary
  • Fluorescent Dyes
  • Nerve Tissue Proteins
  • P2RX2 protein, human
  • P2RX4 protein, human
  • P2RX7 protein, human
  • P2rx2 protein, mouse
  • P2rx4 protein, mouse
  • P2rx7 protein, mouse
  • Quinolinium Compounds
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X2
  • Receptors, Purinergic P2X4
  • Receptors, Purinergic P2X7
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • YO-PRO 1
  • Serotonin
  • Meglumine
  • Adenosine Triphosphate