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 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.
Mesh Terms:
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
Neuron
Date: Aug. 14, 2008
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