Advanced search

Sodium channel Nav1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves

(2017) JOURNAL OF NEUROSCIENCE. 37(20). p.5204-5214
Author
Organization
Abstract
Voltage-gated sodium (Na-V) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine NaV channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na(V)1.1-Na(V)1.4, Na(V)1.6-Na(V)1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na(V)1.8 and Na(V)1.9) inhibited by millimolar concentrations, with Na(V)1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na-V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys(Macacanemestrina). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16% of the baseline. In contrast, >30% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na(V)1.9(-/-) mice. In nerves from Na(V)1.8(-/-) mice, TTX-r C-CAPs could not be detected. These data indicate that Na(V)1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na(V)1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na(V)1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin.
Keywords
nociceptor, nonhuman primate, pain, sodium channels, GUINEA-PIG CORNEA, PRIMARY AFFERENT-FIBERS, DORSAL-ROOT GANGLIA, TETRODOTOXIN-RESISTANT, SENSORY NEURONS, DRG NEURONS, PAINFUL NEUROPATHY, ELECTRICAL-ACTIVITY, UNMYELINATED AXONS, INFLAMMATORY PAIN

Citation

Please use this url to cite or link to this publication:

Chicago
Klein, Amanda H, Alina Vyshnevska, Timothy V Hartke, Roberto De Col, Joseph L Mankowski, Brian Turnquist, Frank Bosmans, et al. 2017. “Sodium Channel Nav1.8 Underlies TTX-resistant Axonal Action Potential Conduction in Somatosensory C-fibers of Distal Cutaneous Nerves.” Journal of Neuroscience 37 (20): 5204–5214.
APA
Klein, A. H., Vyshnevska, A., Hartke, T. V., De Col, R., Mankowski, J. L., Turnquist, B., Bosmans, F., et al. (2017). Sodium channel Nav1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves. JOURNAL OF NEUROSCIENCE, 37(20), 5204–5214.
Vancouver
1.
Klein AH, Vyshnevska A, Hartke TV, De Col R, Mankowski JL, Turnquist B, et al. Sodium channel Nav1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves. JOURNAL OF NEUROSCIENCE. 2017;37(20):5204–14.
MLA
Klein, Amanda H, Alina Vyshnevska, Timothy V Hartke, et al. “Sodium Channel Nav1.8 Underlies TTX-resistant Axonal Action Potential Conduction in Somatosensory C-fibers of Distal Cutaneous Nerves.” JOURNAL OF NEUROSCIENCE 37.20 (2017): 5204–5214. Print.
@article{8584504,
  abstract     = {Voltage-gated sodium (Na-V) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine NaV channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (Na(V)1.1-Na(V)1.4, Na(V)1.6-Na(V)1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (Na(V)1.8 and Na(V)1.9) inhibited by millimolar concentrations, with Na(V)1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different Na-V channel isoforms are distributed along the peripheral and central branches of their bifurcated axons. To determine the relative contribution of TTX-s and TTX-r channels to action potential conduction in different axonal compartments, we investigated the effects of TTX on C-fiber-mediated compound action potentials (C-CAPs) of proximal and distal peripheral nerve segments and dorsal roots from mice and pigtail monkeys(Macacanemestrina). In the dorsal roots and proximal peripheral nerves of mice and nonhuman primates, TTX reduced the C-CAP amplitude to 16\% of the baseline. In contrast, {\textrangle}30\% of the C-CAP was resistant to TTX in distal peripheral branches of monkeys and WT and Na(V)1.9(-/-) mice. In nerves from Na(V)1.8(-/-) mice, TTX-r C-CAPs could not be detected. These data indicate that Na(V)1.8 is the primary isoform underlying TTX-r conduction in distal axons of somatosensory C-fibers. Furthermore, there is a differential spatial distribution of Na(V)1.8 within C-fiber axons, being functionally more prominent in the most distal axons and terminal regions. The enrichment of Na(V)1.8 in distal axons may provide a useful target in the treatment of pain of peripheral origin.},
  author       = {Klein, Amanda H and Vyshnevska, Alina and Hartke, Timothy V and De Col, Roberto and Mankowski, Joseph L and Turnquist, Brian and Bosmans, Frank and Reeh, Peter W and Schmelz, Martin and Carr, Richard W and Ringkamp, Matthias},
  issn         = {0270-6474},
  journal      = {JOURNAL OF NEUROSCIENCE},
  language     = {eng},
  number       = {20},
  pages        = {5204--5214},
  title        = {Sodium channel Nav1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.3799-16.2017},
  volume       = {37},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: