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Received December 18, 2003
Revised January 26, 2004
Accepted after revision February 16, 2004
1 The Johns Hopkins University School of Medicine
2 University of Maryland School of Medicine, Baltimore MD
* To whom correspondence should be addressed. E-mail: bundem{at}jhmi.edu.
An ex vivo, vagally innervated, lung preparation was used to address the hypothesis that vagal C-fibers comprise at least two distinct phenotypes. Histological and extracellular electrophysiological experiments revealed that vagal C-fibers innervating the pulmonary system are derived from cell bodies situated in two distinct vagal sensory ganglia. The jugular (superior) ganglion neurons project C-fibers to both the extrapulmonary airways (larynx, trachea and bronchus) as well as to the lung parenchymal tissue. By contrast, C-fibers from nodose (inferior) neurons innervate primarily structures within the lungs. Histologically, nodose neurons projecting lung C-fibers were different from the jugular neurons in that they were significantly less likely to express neurokinins. The nerve terminals within the lungs of both nodose and jugular C-fibers responded with action potential discharge to capsaicin and bradykinin application, but only the nodose C-fiber population responded with action potential discharge to the P2X selective receptor agonist 
,
-methelyne-ATP. Whole cell patch clamp recording of capsaicin-sensitive nodose and jugular ganglion neurons retrogradely labeled from the lung tissue revealed that, like the nerve terminals, lung specific nodose C-fiber neurons express functional P2X receptors, whereas lung specific jugular C-fibers do not. The data support the hypothesis that both neural crest derived-neurons (jugular ganglia) and placode-derived neurons (nodose ganglia) project C-fibers in the vagus, and that these two C-fiber populations represent distinct phenotypes.
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