Activation of Transient Receptor Potential Vanilloid 1 (TRPV1) by Resiniferatoxin

J Physiol. 2005 Sep 15;567(Pt 3):771-86. doi: 10.1113/jphysiol.2005.087874. Epub 2005 Jul 21.


Transient receptor potential vanilloid 1 (TRPV1) is a Ca(2+) permeable non-selective cation channel activated by physical and chemical stimuli. Resiniferatoxin (RTX), an ultrapotent agonist of TRPV1, is under investigation for treatment of urinary bladder hyper-reflexia and chronic pain conditions. Here, we have determined the characteristics of RTX-induced responses in cells expressing native and cloned rat TRPV1. Whole-cell currents increase with repeated application of submaximal concentrations of RTX until a maximal response is attained and do not deactivate even after prolonged washout. Interestingly, the rate of activation and block by capsazepine of RTX-induced currents are significantly slower than for capsaicin-induced currents. RTX-induced whole-cell currents are outwardly rectifying, but to a lesser extent than capsaicin-induced currents. RTX-induced single channel currents exhibit multiple conductance states and outward rectification. The open probability (P(o)) of RTX-induced currents is higher at all potentials as compared to capsaicin-induced currents, which showed a strong voltage-dependent decrease at negative potentials. Single-channel kinetic analyses reveal that open-time distribution of RTX-induced currents can be fitted with three exponential components at negative and positive potentials. The areas of distribution of the longer open time constants are significantly larger than capsaicin-induced currents. The closed-time distribution of RTX-induced currents can be fitted with three exponential components as compared to capsaicin-induced currents, which require four exponential components. Current-clamp experiments reveal that low concentrations of RTX caused a slow and sustained depolarization beyond threshold while generating few action potentials. Concentrations of capsaicin required for the same extent of depolarization generated a significantly greater number of action potentials. These properties of RTX may play a role in its clinical usefulness.

Publication types

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

MeSH terms

  • Animals
  • Capsaicin / pharmacology
  • Diterpenes / antagonists & inhibitors
  • Diterpenes / pharmacology*
  • Ganglia, Spinal / physiology
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Rats
  • TRPV Cation Channels / agonists*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Transfection
  • Xenopus


  • Diterpenes
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • resiniferatoxin
  • Capsaicin