Long-term diabetic microenvironment augments the decay rate of capsaicin-induced currents in mouse dorsal root ganglion neurons

Xingjuan Chen, Yaqian Duan, Ashley M. Riley, Megan A. Welch, Fletcher White, Maria B. Grant, Alexander Obukhov

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Individuals with end-stage diabetic peripheral neuropathy present with decreased pain sensation. Transient receptor potential vanilloid type 1 (TRPV1) is implicated in pain signaling and resides on sensory dorsal root ganglion (DRG) neurons. We investigated the expression and functional activity of TRPV1 in DRG neurons of the Ins2 +/Akita mouse at 9 months of diabetes using immunohistochemistry, live single cell calcium imaging, and whole-cell patch-clamp electrophysiology. 2 0 ,7 0 -Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence assay was used to determine the level of Reactive Oxygen Species (ROS) in DRGs. Although TRPV1 expressing neuron percentage was increased in Ins2 +/Akita DRGs at 9 months of diabetes compared to control, capsaicin-induced Ca 2+ influx was smaller in isolated Ins2 +/Akita DRG neurons, indicating impaired TRPV1 function. Consistently, capsaicin-induced Ca 2+ influx was decreased in control DRG neurons cultured in the presence of 25 mM glucose for seven days versus those cultured with 5.5 mM glucose. The high glucose environment increased cytoplasmic ROS accumulation in cultured DRG neurons. Patch-clamp recordings revealed that capsaicin-activated currents decayed faster in isolated Ins2 +/Akita DRG neurons as compared to those in control neurons. We propose that in poorly controlled diabetes, the accelerated rate of capsaicin-sensitive TRPV1 current decay in DRG neurons decreases overall TRPV1 activity and contributes to peripheral neuropathy.

Original languageEnglish (US)
Article number775
JournalMolecules
Volume24
Issue number4
DOIs
StatePublished - Feb 21 2019

Fingerprint

Capsaicin
Induced currents
Spinal Ganglia
neurons
decay rates
Neurons
mice
Medical problems
glucose
clamps
pain
Diagnosis-Related Groups
Clamping devices
Peripheral Nervous System Diseases
Glucose
Reactive Oxygen Species
electrophysiology
Sensory Ganglia
Electrophysiology
Pain

Keywords

  • Calcium influx
  • Capsaicin
  • DRG neurons
  • Ins2 mouse
  • ROS
  • TRPV1

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Long-term diabetic microenvironment augments the decay rate of capsaicin-induced currents in mouse dorsal root ganglion neurons. / Chen, Xingjuan; Duan, Yaqian; Riley, Ashley M.; Welch, Megan A.; White, Fletcher; Grant, Maria B.; Obukhov, Alexander.

In: Molecules, Vol. 24, No. 4, 775, 21.02.2019.

Research output: Contribution to journalArticle

Chen, Xingjuan ; Duan, Yaqian ; Riley, Ashley M. ; Welch, Megan A. ; White, Fletcher ; Grant, Maria B. ; Obukhov, Alexander. / Long-term diabetic microenvironment augments the decay rate of capsaicin-induced currents in mouse dorsal root ganglion neurons. In: Molecules. 2019 ; Vol. 24, No. 4.
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