Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

J Neurophysiol. 2013 Apr;109(7):1704-12. doi: 10.1152/jn.00012.2013. Epub 2013 Jan 9.


QX-314 (N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of "pore dilation" previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50-100 μM. We conclude that QX-314 is directly permeant in the "standard" pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Capsaicin / pharmacology
  • Cell Line, Tumor
  • Cesium / pharmacology
  • Connexins / metabolism
  • Ganglia, Spinal / cytology
  • Humans
  • Ion Transport / drug effects*
  • Lidocaine / analogs & derivatives*
  • Lidocaine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sodium / metabolism
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / metabolism*


  • Connexins
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Cesium
  • QX-314
  • Lidocaine
  • Sodium
  • Capsaicin