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

We developed an isolated tracheally perfused (35-37degreesC) 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 (I ym) while C-fibres with conduction velocities between 0.7 and 1.5 m s(-1) were capsaicin insensitive. Similarly, bradykinin (1muM) excited only those C-fibres with conduction velocities < 0.7 m s(-1). The response to bradykinin was not mimicked by the beta(1) receptor agonist [des-Arg(9)]bradykinin (1 mum) and was abolished by the bradykinin beta(2) receptor antagonist HOE 140 (1 mum). Adenosine 5'-triphosphate (ATP, 30 muM) activated the C-fibres irrespective of the conduction velocities. This response was mimicked by the selective P2X agonist alpha,beta-methylene-adenosine 5'-triphosphate (30,am). Consistent with the electrophysiology, morphological analysis revealed that only similar to40 % of the lung-specific small diameter (< 20 ym) JNC neurons consistent with the C-fibre cell bodies display VRI 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.