The basal thermal sensitivity of the TRPV1 ion channel is determined by PKCβII

J Neurosci. 2014 Jun 11;34(24):8246-58. doi: 10.1523/JNEUROSCI.0278-14.2014.


Peripheral nociceptors are excited by the activation of membrane receptors and ion channels. The heat-sensitive TRPV1 ion channel responds to various noxious chemical and thermal stimuli, causing pain and itch. Here, we show that TRPV1 is coexpressed with PKCβII in a subset of mouse sensory neurons and that, in these neurons, TRPV1 binds directly to PKCβII, leading to the activation and translocation of PKCβII. Activated PKCβII, in turn, significantly increases the responsiveness of TRPV1 by phosphorylating Thr705. The heat sensitivity of TRPV1 is almost eliminated by either knocking down PKCβII or mutating Thr705; however, neither of these manipulations affects the potentiation of TRPV1 caused by the activation of PKCε. PKCβII thus acts as an auxiliary subunit of TRPV1 by forming a population-dependent TRPV1 ion channel complex controlling the sensitivity of TRPV1 and setting the threshold for pain and itch.

Keywords: PKC; TRP ion channels; TRPV1; auxiliary subunit; pain; phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Down-Regulation / physiology
  • Female
  • Ganglia, Spinal / cytology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hot Temperature*
  • Humans
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Phosphorylation
  • Protein Binding / genetics
  • Protein Kinase C beta / metabolism*
  • Rats
  • Rats, Wistar
  • Sensory System Agents / pharmacology
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • Sensory System Agents
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Green Fluorescent Proteins
  • Protein Kinase C beta
  • Capsaicin