ArticleMolecular pharmacology2014
Sensory nerve terminal mitochondrial dysfunction induces hyperexcitability in airway nociceptors via protein kinase C.
Article in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
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- Network pharmacology-based dissection of the underlying mechanisms of dyspnoea induced by zedoary turmeric oil.Basic & clinical pharmacology & toxicology · 2022Article
- Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice.Neuroscience bulletin · 2022Article
- PACAP-38 Induces Transcriptomic Changes in Rat Trigeminal Ganglion Cells Related to Neuroinflammation and Altered Mitochondrial Function Presumably via PAC1/VPAC2 Receptor-Independent Mechanism.International journal of molecular sciences · 2022Article
- Macrophages and glial cells: Innate immune drivers of inflammatory arthritic pain perception from peripheral joints to the central nervous system.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Mitochondria and sensory processing in inflammatory and neuropathic pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Nociceptors: Their Role in Body's Defenses, Tissue Specific Variations and Anatomical Update.Journal of pain research · 2022Review
- Anti-Malignant Ascites Effect of Total Diterpenoids fromMolecules (Basel, Switzerland) · 2021Article
- A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction.Brain, behavior, and immunity · 2020Article
- Antimycin A increases bronchopulmonary C-fiber excitability via protein kinase C alpha.Respiratory physiology & neurobiology · 2020Article
- Article
- Antimycin A-induced mitochondrial dysfunction activates vagal sensory neurons via ROS-dependent activation of TRPA1 and ROS-independent activation of TRPV1.Brain research · 2019Article
- NOX2-Dependent Reactive Oxygen Species Regulate Formyl-Peptide Receptor 1-Mediated TrkA Transactivation in SH-SY5Y Cells.Oxidative medicine and cellular longevity · 2019Article
- Mechanistic link between diesel exhaust particles and respiratory reflexes.The Journal of allergy and clinical immunology · 2018Article
- Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature.Molecular neuropsychiatry · 2017Review
- Role of reactive oxygen species and TRP channels in the cough reflex.Cell calcium · 2016Review
- TRP channels and traffic-related environmental pollution-induced pulmonary disease.Seminars in immunopathology · 2016Review
- Oxidative stress as activators of sensory nerves for cough.Pulmonary pharmacology & therapeutics · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Airway sensory nerve excitability is a key determinant of respiratory disease-associated reflexes and sensations such as cough and dyspnea. Inflammatory signaling modulates mitochondrial function and produces reactive oxygen species (ROS). Peripheral terminals of sensory nerves are densely packed with mitochondria; thus, we hypothesized that mitochondrial modulation would alter neuronal excitability. We recorded action potential firing from the terminals of individual bronchopulmonary C-fibers using a mouse ex vivo lung-vagal ganglia preparation. C-fibers were characterized as nociceptors or non-nociceptors based upon conduction velocity and response to transient receptor potential (TRP) channel agonists. Antimycin A (mitochondrial complex III Qi site inhibitor) had no effect on the excitability of non-nociceptors. However, antimycin A increased excitability in nociceptive C-fibers, decreasing the mechanical threshold by 50% and increasing the action potential firing elicited by a P2X2/3 agonist to 270% of control. Antimycin A-induced nociceptor hyperexcitability was independent of TRP ankyrin 1 or TRP vanilloid 1 channels. Blocking mitochondrial ATP production with oligomycin or myxothiazol had no effect on excitability. Antimycin A-induced hyperexcitability was dependent on mitochondrial ROS and was blocked by intracellular antioxidants. ROS are known to activate protein kinase C (PKC). Antimycin A-induced hyperexcitability was inhibited by the PKC inhibitor bisindolylmaleimide (BIM) I, but not by its inactive analog BIM V. In dissociated vagal neurons, antimycin A caused ROS-dependent PKC translocation to the membrane. Finally, H2O2 also induced PKC-dependent nociceptive C-fiber hyperexcitability and PKC translocation. In conclusion, ROS evoked by mitochondrial dysfunction caused nociceptor hyperexcitability via the translocation and activation of PKC.
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Registered trials
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