{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:23:04Z","timestamp":1787016184590,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      The influence of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 on inflammatory mediator\u2010induced activation of airway vagal nodose C\u2010fibres was evaluated by comparing responses in wild\u2010type\n                      <jats:italic>versus<\/jats:italic>\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010\/\u2010 mice. A single\u2010cell RT\u2010PCR analysis indicated that virtually all nodose C\u2010fibre neurons expressed Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 (SCN11A) mRNA. Using extracellular electrophysiological recordings in an isolated vagally innervated mouse trachea\u2013lung preparation, it was noted that mediators acting via G protein\u2010coupled receptors (PAR2), or ionotropic receptors (P2\u00d73) were 70\u201385% less effective in evoking action potential discharge in the absence of Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9. However, there was no difference in action potential discharge between wild\u2010type and Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010\/\u2010 when the stimulus was a rapid punctate mechanical stimulus. An analysis of the passive and active properties of isolated nodose neurons revealed no difference between neurons from wild\u2010type and Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010\/\u2010 mice, with the exception of a modest difference in the duration of the afterhyperpolarization. There was also no difference in the amount of current required to evoke action potentials (rheobase) or the action potential voltage threshold. The inward current evoked by the chemical mediator by a P2\u00d73 agonist was the same in wild\u2010type\n                      <jats:italic>versus<\/jats:italic>\n                      Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9\u2010\/\u2010 neurons. However, the current was sufficient to evoke action potential only in the wild\u2010type neurons. The data support the speculation that Na\n                      <jats:sub>V<\/jats:sub>\n                      1.9 could be an attractive therapeutic target for inflammatory airway disease by selectively inhibiting inflammatory mediator\u2010associated vagal C\u2010fibre activation.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15441-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Inflammatory mediators were much less effective in activating the terminals of vagal airway C\u2010fibres in mice lacking Na\n                            <jats:sub>V<\/jats:sub>\n                            1.9.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            The active and passive properties of nodose neurons were the same between wild\u2010type neurons and Na\n                            <jats:sub>V<\/jats:sub>\n                            1.9\u2010\/\u2010 neurons.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Nerves lacking Na\n                            <jats:sub>V<\/jats:sub>\n                            1.9 responded, normally, with action potential discharge to rapid punctate mechanical stimulation of the terminals or the rapid stimulation of the cell bodies with inward current injections.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Na\n                            <jats:sub>V<\/jats:sub>\n                            1.9 channels could be an attractive target to selectively inhibit vagal nociceptive C\u2010fibre activation evoked by inflammatory mediators without blocking the nerves\u2019 responses to the potentially hazardous stimuli associated with aspiration.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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