{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:01:46Z","timestamp":1780333306658,"version":"3.54.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35HL155671"],"award-info":[{"award-number":["R35HL155671"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The purpose of this study was to determine the role of Na<jats:sub>V<\/jats:sub>1.7 in action potential conduction in C\u2010fibres in the bronchial branches of the human vagus nerve.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Bronchial branches of the vagus nerve were dissected from human donor tissue. The C\u2010wave of the electrically evoked compound action potential was quantified in the absence and presence of increasing concentrations of the selective Na<jats:sub>V<\/jats:sub>1.7 blocking drugs, PF\u201005089771 and ST\u20102262, as well as the Na<jats:sub>V<\/jats:sub>1.1, 1.2, and 1.3 blocking drug ICA121\u2010431. The efficacy and potency of these inhibitors were compared to the standard Na<jats:sub>V<\/jats:sub>1 blocker, tetrodotoxin. We then compared the relative potencies of the Na<jats:sub>V<\/jats:sub>1 blockers in inhibiting the C\u2010wave 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 Na<jats:sub>V<\/jats:sub>1.7 channels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The selective Na<jats:sub>V<\/jats:sub>1.7 blockers inhibited the C\u2010wave of the compound action potential with potencies similar to that observed in the Na<jats:sub>V<\/jats:sub>1.7 bronchial contractions assay. Using rt\u2010PCR, we noted that Na<jats:sub>V<\/jats:sub>1.7 mRNA was strongly expressed and transported down the vagus nerve bundles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Na<jats:sub>V<\/jats:sub>1.7 blockers can prevent action potential conduction in the majority of vagal C\u2010fibres arising from human bronchi. Blockers of Na<jats:sub>V<\/jats:sub>1.7 channels may therefore have value in inhibiting the responses to excessive airway C\u2010fibre activation in inflammatory airway disease, responses that include coughing as well as reflex bronchoconstriction and secretions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15686","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T19:06:13Z","timestamp":1633979173000},"page":"242-251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Role of Na<sub>V<\/sub>1.7 in action potential conduction along human bronchial vagal afferent C\u2010fibres"],"prefix":"10.1111","volume":"179","author":[{"given":"Marian","family":"Kollarik","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ru","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoleta","family":"Pavelkova","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Physiology University of South Florida  Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Mulcahy","sequence":"additional","affiliation":[{"name":"SiteOne Therapeutics  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hunter","sequence":"additional","affiliation":[{"name":"SiteOne Therapeutics  South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Undem","sequence":"additional","affiliation":[{"name":"Department of Medicine Johns Hopkins School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15539"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152405"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.211bf.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.224204"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135446"},{"key":"e_1_2_11_7_1","first-page":"1","article-title":"Afferent vagal C fibre innervation of the lungs and airways and its functional significance","volume":"99","author":"Coleridge J. 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