Proinflammatory Mediators Modulate the Heat-Activated Ion Channel TRPV1 via the Scaffolding Protein AKAP79/150

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 k...

Full description

Saved in:
Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2008-08, Vol.59 (3), p.450-461
Main Authors: Zhang, Xuming, Li, Lin, McNaughton, Peter A.
Format: Article
Language:English
Subjects:
A Kinase Anchor Proteins - metabolism
Animals
Binding sites
Bradykinin - pharmacology
CELLBIO
Cells, Cultured
Cyclic AMP-Dependent Protein Kinases - physiology
Dinoprostone - pharmacology
Dose-Response Relationship, Radiation
Electric Stimulation - methods
Experiments
Ganglia, Spinal - cytology
Heat
Hot Temperature
Humans
Kinases
Membrane Potentials - drug effects
Membrane Potentials - physiology
Membrane Potentials - radiation effects
Models, Biological
MOLIMMUNO
MOLNEURO
Mutation - physiology
Neurons
Neurons, Afferent - drug effects
Neurons, Afferent - metabolism
Patch-Clamp Techniques
Peptides
Phosphorylation
Protein Binding - drug effects
Protein Kinase C - physiology
Proteins
Rats
RNA, Small Interfering - pharmacology
Signal Transduction - drug effects
Signal Transduction - physiology
Temperature
Transfection
TRPV Cation Channels - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2008.05.015