Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse

We developed an isolated tracheally perfused (35-37°C) nerve-lung preparation for the study of bronchopulmonary afferent nerve activity in the mouse. Extracellular recordings were made from the vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) with identified receptive fields in the lungs. Analysis of the vagal compound action potential revealed that the mouse vagal C-fibre conduction velocities range from 0.3 to 1.5 m s^-1. A total of 83 bronchopulmonary C-fibres were studied. The sensitivity of the bronchopulmonary C-fibres to the vanilloid receptor 1 (VR1) agonist capsaicin was dependent on conduction velocity. Thus C-fibres with conduction velocities between 0.3 and 0.7 m s^-1 responded to capsaicin (1 μM) while C-fibres with conduction velocities between 0.7 and 1.5 m s^-1 were capsaicin insensitive. Similarly, bradykinin (1 μM) excited only those C-fibres with conduction velocities < 0.7 m s^-1. The response to bradykinin was not mimicked by the B₁ receptor agonist [des-Arg⁹]bradykinin (1 μM) and was abolished by the bradykinin B₂ receptor antagonist HOE 140 (1 μM). Adenosine 5′-triphosphate (ATP, 30 μM) activated the C-fibres irrespective of the conduction velocities. This response was mimicked by the selective P2X agonist α,β-methylene-adenosine 5′-triphosphate (30 μM). Consistent with the electrophysiology, morphological analysis revealed that only ∼40% of the lung-specific small diameter (< 20 μM) JNC neurons consistent with the C-fibre cell bodies display VR1 immunoreactivity. This study describes a convenient in vitro method for the study of mouse bronchopulmonary C-fibres. The results indicate that C-fibres in the mouse lungs are not homogeneous, but can be subclassified into capsaicin-sensitive and capsaicin-insensitive phenotypes.