Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse.
We developed an isolated tracheally perfused (35-37 degrees 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 microM) while C-fibres with conduction velocities between 0.7 and 1.5 m s(-1) were capsaicin insensitive. Similarly, bradykinin (1 microM) 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 microM) and was abolished by the bradykinin B2 receptor antagonist HOE 140 (1 microM). Adenosine 5'-triphosphate (ATP, 30 microM) 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 microM). Consistent with the electrophysiology, morphological analysis revealed that only approximately 40% of the lung-specific small diameter (< 20 microm) 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.
Kollarik
Marian
M
Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Dinh
Q Thai
QT
Fischer
Axel
A
Undem
Bradley J
BJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000294:innervation*; D002211:Capsaicin / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036421:Nerve Fibers, Unmyelinated / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D009475:Neurons, Afferent / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D010812:Physical Stimulation; D011955:Receptors, Drug / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D011955:Receptors, Drug; D002211:Capsaicin