RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose

PloS One
Doris LamVerónica A Campanucci

Abstract

Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which is the most common complication that affects approximately 50% of diabetic patients. Yet, the underlying mechanisms linking hyperglycemia and symptoms of DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such sensory abnormalities and shows elevated expression levels in animal models of diabetes. Here, we investigated the function of TRPV1 channels in sensory neurons cultured from the dorsal root ganglion (DRG) of neonatal mice, under control (5mM) and high glucose (25mM) conditions. After maintaining DRG neurons in high glucose for 1 week, we observed a significant increase in capsaicin (CAP)-evoked currents and CAP-evoked depolarizations, independent of TRPV1 channel expression. These functional changes were largely dependent on the expression of the receptor for Advanced Glycation End-products (RAGE), calcium influx, cytoplasmic ROS accumulation, PKC, and Src kinase activity. Like cultured neurons from neonates, mature neurons from...Continue Reading

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Citations

Jun 23, 2018·Journal of Cell Science·Samuel M BestallLucy F Donaldson
Feb 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xingjuan ChenAlexander G Obukhov
Nov 23, 2020·Physiology & Behavior·Zeinab MomeniVerónica A Campanucci
Oct 22, 2021·Diabetic Medicine : a Journal of the British Diabetic Association·Di YePeter D Drummond

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Methods Mentioned

BETA
enzymatic dissociation
transgenic
biopsies

Software Mentioned

Axiovision
Zen
Prism
pCLAMP
Graphpad InStat
ImageJ
GraphPad
Origin

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