Assessing NaV1.7 during tonic firing in pig C-nociceptors
Assuming the voltage-gated sodium channel (VGSC) NaV1.7 facilitates action potential generation upon slow electrical depolarization, we investigated protoxin II and TTX to target VGSC sub-types and to assess their role in C-fiber excitability when stimulated with sinusoidal single 1 Hz pulse (500 ms...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 3, 2025
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| In: |
PLOS ONE
Year: 2025, Volume: 20, Issue: 12, Pages: 1-14 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0335081 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1371/journal.pone.0335081 Verlag, kostenfrei, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0335081 
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| Author Notes: | Sabrina Soares, Martin Schmelz, Richard Carr, Kyra Sohns, Roman Rukwied |
| Summary: | Assuming the voltage-gated sodium channel (VGSC) NaV1.7 facilitates action potential generation upon slow electrical depolarization, we investigated protoxin II and TTX to target VGSC sub-types and to assess their role in C-fiber excitability when stimulated with sinusoidal single 1 Hz pulse (500 ms) and repetitive 4 Hz stimuli. We performed ex vivo extracellular compound potentials (CAP) recordings of pig saphenous nerve and in vivo pig single nerve fiber (SNF) recordings of heat- mechanosensitive (“polymodal”) nociceptors (C-HT) and low- threshold mechanoresponsive C-fibers (C-LTMR) upon electrical 1 and 4 Hz sinusoidal stimulation, which evoke a discharge burst and a tonic response, respectively. Both toxins reduced C-CAP amplitudes and conduction velocity. Number of action potentials evoked by low-intensity phasic (1 Hz) or tonic (4 Hz) sinusoidal stimulation were reduced in C-HT nociceptors after protoxin. In C-LTMR fibers, protoxin reduced the number of action potentials to 4 Hz, but did not affect 1 Hz discharges. The toxins did not increase the delay of action potential initiation of C-CAPs or during SNF. Our results confirm the functional role of NaV1.7 to tonic supra-threshold electrical 4 Hz sinusoidal action potential firing in C-fibers. Protoxin reduced AP discharges to low-intensity phasic 1 Hz stimuli in C-HT nociceptors but not C-LTMR touch fibers. This finding suggests a differential functional role of NaV1.7 between C-fiber classes. Peripheral NaV1.7 blockade seems to increase the depolarization level required for C-nociceptor activation, and this might be relevant to target clinically ongoing pain. |
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| Item Description: | Gesehen am 22.01.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0335081 |