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Received February 21, 2003
Accepted after revision June 11, 2003
1 Johns Hopkins University School of Medicine, Baltimore, MD, USA
2 Charité School of Medicine, Humboldt University Berlin, Germany
3 Johns Hopkins Asthma Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
* To whom correspondence should be addressed. E-mail: bundem{at}jhmi.edu.
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 of between 0.3 and 0.7 m s-1 responded to capsaicin (1 µM) while C-fibres with conduction velocities of 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 
,
-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.
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