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To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1113/jphysiol.2007.146365 Byline: Kevin Kwong (1), Michael J. Carr (2), Anna Gibbard (2), Tony J. Savage (3), Kuljit Singh (3), Junping Jing (2), Sonya Meeker (1), Bradley J. Undem (1) Abstract: Lung vagal sensory fibres are broadly categorized as C fibres (nociceptors) and A fibres (non-nociceptive; rapidly and slowly adapting low-threshold stretch receptors). These afferent fibre types differ in degree of myelination, conduction velocity, neuropeptide content, sensitivity to chemical and mechanical stimuli, as well as evoked reflex responses. Recent studies in nociceptive fibres of the somatosensory system indicated that the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels (VGSC) are preferentially expressed in the nociceptive fibres of the somatosensory system (dorsal root ganglia). Whereas TTX-R sodium currents have been documented in lung vagal sensory nerves fibres, a rigorous comparison of their expression in nociceptive versus non-nociceptive vagal sensory neurons has not been carried out. Using multiple approaches including patch clamp electrophysiology, immunohistochemistry, and single-cell gene expression analysis in the guinea pig, we obtained data supporting the hypothesis that the TTX-R sodium currents are similarly distributed between nodose ganglion A-fibres and C-fibres innervating the lung. Moreover, mRNA and immunoreactivity for the TTX-R VGSC molecules Na.sub.V1.8 and Na.sub.V1.9 were present in nearly all neurons. We conclude that contrary to findings in the somatosensory neurons, TTX-R VGSCs are not preferentially expressed in the nociceptive C-fibre population innervating the lungs. Author Affiliation: (1)Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA (2)GlaxoSmithKline, King of Prussia, PA, USA (3)Stevenage, UK Article History: (Received 11 October 2007; accepted after revision 3 January 2008; first published online 10 January 2008) Article note: Corresponding author B. J. Undem: Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. Email: bundem@jhmi.edu