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

Xuming Zhang, Lin Li, Peter A McNaughton

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)450-61
Number of pages12
JournalNeuron
Volume59
Issue number3
DOIs
Publication statusPublished - 14 Aug 2008

Keywords

  • A Kinase Anchor Proteins
  • Animals
  • Bradykinin
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Ganglia, Spinal
  • Hot Temperature
  • Humans
  • Membrane Potentials
  • Models, Biological
  • Mutation
  • Neurons, Afferent
  • Patch-Clamp Techniques
  • Protein Binding
  • Protein Kinase C
  • RNA, Small Interfering
  • Rats
  • Signal Transduction
  • TRPV Cation Channels
  • Transfection
  • Journal Article
  • Research Support, Non-U.S. Gov't

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