TRPV1 shows dynamic ionic selectivity during agonist stimulation

Nat Neurosci. 2008 May;11(5):555-64. doi: 10.1038/nn.2102. Epub 2008 Apr 6.


Transient receptor potential vanilloid 1 (TRPV1) is an ion channel that is gated by noxious heat, capsaicin and other diverse stimuli. It is a nonselective cation channel that prefers Ca2+ over Na+. These permeability characteristics, as in most channels, are widely presumed to be static. On the contrary, we found that activation of native or recombinant rat TRPV1 leads to time- and agonist concentration-dependent increases in relative permeability to large cations and changes in Ca2+ permeability. Using the substituted cysteine accessibility method, we saw that these changes were attributable to alterations in the TRPV1 selectivity filter. TRPV1 agonists showed different capabilities for evoking ionic selectivity changes. Furthermore, protein kinase C-dependent phosphorylation of Ser800 in the TRPV1 C terminus potentiated agonist-evoked ionic selectivity changes. Thus, the qualitative signaling properties of TRPV1 are dynamically modulated during channel activation, a process that probably shapes TRPV1 participation in pain, cytotoxicity and neurotransmitter release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Capsaicin / pharmacology
  • Cell Line
  • Cell Membrane Permeability / drug effects
  • Cell Membrane Permeability / genetics*
  • Cells, Cultured
  • Humans
  • Inflammation Mediators / pharmacology
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / physiology*
  • Ions / metabolism*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Nociceptors / drug effects
  • Nociceptors / metabolism*
  • Pain / chemically induced
  • Pain / genetics
  • Pain / metabolism
  • Patch-Clamp Techniques
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Sensory System Agents / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Time Factors


  • Inflammation Mediators
  • Ions
  • Sensory System Agents
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Protein Kinase C
  • Capsaicin