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

Xuming Zhang, Lin Li, Peter A. McNaughton*

*Corresponding author for this work

Research output: Contribution to journalArticle

186 Citations (Scopus)
4 Downloads (Pure)

Abstract

The ability of vertebrates to detect and avoid damaging extremes of temperature depends on activation of ion channels belonging to the thermo-TRIP 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)450-461
Number of pages12
JournalNeuron
Volume59
Issue number3
DOIs
Publication statusPublished - 14 Aug 2008

Keywords

  • capsaicin receptor VR1
  • root ganglion neurons
  • vanilloid receptor-1
  • kinase-II
  • direct phosphorylation
  • thermal hyperalgesia
  • nociceptive neurons
  • evoked activation
  • sensory neurons
  • desensitization

Cite this

Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. / Zhang, Xuming; Li, Lin; McNaughton, Peter A.

In: Neuron, Vol. 59, No. 3, 14.08.2008, p. 450-461.

Research output: Contribution to journalArticle

Zhang, Xuming ; Li, Lin ; McNaughton, Peter A. / Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. In: Neuron. 2008 ; Vol. 59, No. 3. pp. 450-461.
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