Abstract
Background and Purpose: The purpose of this study was to determine the role of NaV1.7 in action potential conduction in C-fibres in the bronchial branches of the human vagus nerve. Experimental Approach: Bronchial branches of the vagus nerve were dissected from human donor tissue. The C-wave of the electrically evoked compound action potential was quantified in the absence and presence of increasing concentrations of the selective NaV1.7 blocking drugs, PF-05089771 and ST-2262, as well as the NaV1.1, 1.2, and 1.3 blocking drug ICA121-431. The efficacy and potency of these inhibitors were compared to the standard NaV1 blocker, tetrodotoxin. We then compared the relative potencies of the NaV1 blockers in inhibiting the C-wave of the compound action potential, with their ability to inhibit parasympathetic cholinergic contraction of human isolated bronchi, a response previously shown to be strictly dependent on NaV1.7 channels. Key Results: The selective NaV1.7 blockers inhibited the C-wave of the compound action potential with potencies similar to that observed in the NaV1.7 bronchial contractions assay. Using rt-PCR, we noted that NaV1.7 mRNA was strongly expressed and transported down the vagus nerve bundles. Conclusions and Implications: NaV1.7 blockers can prevent action potential conduction in the majority of vagal C-fibres arising from human bronchi. Blockers of NaV1.7 channels may therefore have value in inhibiting the responses to excessive airway C-fibre activation in inflammatory airway disease, responses that include coughing as well as reflex bronchoconstriction and secretions.
Original language | English (US) |
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Pages (from-to) | 242-251 |
Number of pages | 10 |
Journal | British Journal of Pharmacology |
Volume | 179 |
Issue number | 2 |
DOIs | |
State | Published - Jan 2022 |
ASJC Scopus subject areas
- Pharmacology