Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150

Neuron. 2008 Aug 14;59(3):450-61. doi: 10.1016/j.neuron.2008.05.015.


The ability of vertebrates to detect and avoid damaging extremes of temperature depends on activation of ion channels belonging to the thermo-TRP family. Injury or inflammation causes the release of inflammatory mediators which lower the threshold for detection of painful levels of heat, a process known as heat hyperalgesia. These inflammatory mediators act by at least three distinct intracellular signaling pathways. Here, we show that modulation of the sensitivity of the heat-activated ion channel TRPV1 by the protein kinases PKA and PKC and by the phosphatase calcineurin depends on the formation of a signaling complex between these enzymes, the scaffolding protein AKAP79/150 and TRPV1. We identify a critical region in the TRPV1 C-terminal which mediates binding of AKAP79/150. If binding is prevented, then sensitization by both bradykinin and PGE(2) is abrogated. AKAP79/150 is therefore a final common element in heat hyperalgesia, on which the effects of multiple proinflammatory mediators converge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / metabolism*
  • Animals
  • Bradykinin / pharmacology
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Dinoprostone / pharmacology
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Ganglia, Spinal / cytology
  • Hot Temperature*
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Models, Biological
  • Mutation / physiology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism*
  • Patch-Clamp Techniques
  • Protein Binding / drug effects
  • Protein Kinase C / physiology
  • RNA, Small Interfering / pharmacology
  • Rats
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TRPV Cation Channels / metabolism*
  • Transfection


  • A Kinase Anchor Proteins
  • Akap5 protein, rat
  • RNA, Small Interfering
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Dinoprostone
  • Bradykinin