Mitochondrial modulation-induced activation of vagal sensory neuronal subsets by antimycin A, but not CCCP or rotenone, correlates with mitochondrial superoxide production

Inflammation causes nociceptive sensory neuron activation, evoking debilitating symptoms and reflexes. Inflammatory signaling pathways are capable of modulating mitochondrial function, resulting in reactive oxygen species (ROS) production, mitochondrial depolarization and calcium release. Previously...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2018-05, Vol.13 (5), p.e0197106
Main Authors: Stanford, Katherine R, Taylor-Clark, Thomas E
Format: Article
Language:English
Subjects:
Action Potentials
Activation
Ankyrins
Antimycin A
Antimycin A - administration & dosage
Binding sites
Biology and Life Sciences
Calcium
Calcium (mitochondrial)
Calcium - metabolism
Capsaicin receptors
Carbonyl Cyanide m-Chlorophenyl Hydrazone
Carbonyls
Chemical inhibitors
Correlation
Cyanides
Depolarization
Electron transport chain
Fibers
Fluxes
Health aspects
Humans
Hydrazones
Inflammation
Inflammation - genetics
Inflammation - metabolism
Inflammation - pathology
Inhibitors
Kinases
Medicine and Health Sciences
Mitochondria
Mitochondria - pathology
Mitochondrial DNA
Modulation
Morphology
Neurons
Nociceptors - metabolism
Nociceptors - pathology
Oxygen
Pain
Pain perception
Physical Sciences
Physiology
Reactive oxygen species
Reactive Oxygen Species - metabolism
Reflexes
Rodents
Rotenone
Rotenone - administration & dosage
Sensory Receptor Cells - metabolism
Sensory Receptor Cells - pathology
Signal Transduction
Superoxide
Superoxides
Superoxides - metabolism
Transient receptor potential proteins
TRPA1 Cation Channel - genetics
TRPA1 Cation Channel - metabolism
TRPV Cation Channels - genetics
TRPV Cation Channels - metabolism
Vagus nerve
Vagus Nerve - metabolism
Vagus Nerve - physiopathology
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:Inflammation causes nociceptive sensory neuron activation, evoking debilitating symptoms and reflexes. Inflammatory signaling pathways are capable of modulating mitochondrial function, resulting in reactive oxygen species (ROS) production, mitochondrial depolarization and calcium release. Previously we showed that mitochondrial modulation with antimycin A, a complex III inhibitor, selectively stimulated nociceptive bronchopulmonary C-fibers via the activation of transient receptor potential (TRP) ankyrin 1 (A1) and vanilloid 1 (V1) cation channels. TRPA1 is ROS-sensitive, but there is little evidence that TRPV1 is activated by ROS. Here, we used dual imaging of dissociated vagal neurons to investigate the correlation of mitochondrial superoxide production (mitoSOX) or mitochondrial depolarization (JC-1) with cytosolic calcium (Fura-2AM), following mitochondrial modulation by antimycin A, rotenone (complex I inhibitor) and carbonyl cyanide m-chlorophenyl hydrazone (CCCP, mitochondrial uncoupling agent). Mitochondrial modulation by all agents selectively increased cytosolic calcium in a subset of TRPA1/TRPV1-expressing (A1/V1+) neurons. There was a significant correlation between antimycin A-induced calcium responses and mitochondrial superoxide in wild-type 'responding' A1/V1+ neurons, which was eliminated in TRPA1-/- neurons, but not TRPV1-/- neurons. Nevertheless, antimycin A-induced superoxide production did not always increase calcium in A1/V1+ neurons, suggesting a critical role of an unknown factor. CCCP caused both superoxide production and mitochondrial depolarization but neither correlated with calcium fluxes in A1/V1+ neurons. Rotenone-induced calcium responses in 'responding' A1/V1+ neurons correlated with mitochondrial depolarization but not superoxide production. Our data are consistent with the hypothesis that mitochondrial dysfunction causes calcium fluxes in a subset of A1/V1+ neurons via ROS-dependent and ROS-independent mechanisms.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0197106