Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 Function In Vivo

Membrane remodeling by inflammatory mediators influences the function of sensory ion channels. The capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channel contributes to neurogenic inflammation and pain hypersensitivity, in part because of its potentiation downstream o...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2021-01, Vol.41 (3), p.408-423
Main Authors: Caires, Rebeca, Bell, Briar, Lee, Jungsoo, Romero, Luis O, Vásquez, Valeria, Cordero-Morales, Julio F
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
Caenorhabditis elegans - physiology
Caenorhabditis elegans Proteins - biosynthesis
Calcium Signaling - drug effects
Capsaicin
Capsaicin - pharmacology
Capsaicin receptors
Diet
Dietary Supplements
Domains
HEK293 Cells
Humans
Hypersensitivity
In vivo methods and tests
Inflammation
Ion channels
Lipid Metabolism
Lipids
myo-Inositol-1 (or 4)-monophosphatase
Neurons - metabolism
Pain
Pain perception
Phosphatidylinositols - metabolism
Phosphatidylinositols - pharmacology
Phospholipase C
Phosphoric Monoester Hydrolases - deficiency
Potentiation
Receptors
Transient receptor potential proteins
TRPV Cation Channels - genetics
TRPV Cation Channels - physiology
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:Membrane remodeling by inflammatory mediators influences the function of sensory ion channels. The capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channel contributes to neurogenic inflammation and pain hypersensitivity, in part because of its potentiation downstream of phospholipase C-coupled receptors that regulate phosphoinositide lipid content. Here, we determined the effect of phosphoinositide lipids on TRPV1 function by combining genetic dissection, diet supplementation, and behavioral, biochemical, and functional analyses in As capsaicin elicits heat and pain sensations in mammals, transgenic TRPV1 worms exhibit an aversive response to capsaicin. TRPV1 worms with low levels of phosphoinositide lipids display an enhanced response to capsaicin, whereas phosphoinositide lipid supplementation reduces TRPV1-mediated responses. A worm carrying a TRPV1 construct lacking the distal C-terminal domain features an enhanced response to capsaicin, independent of the phosphoinositide lipid content. Our results demonstrate that TRPV1 activity is enhanced when the phosphoinositide lipid content is reduced, and the C-terminal domain is key to determining agonist response .
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0803-20.2020