Ablation of vagal preganglionic neurons innervating the extra-thoracic trachea affects ventilatory responses to hypercapnia and hypoxia.
This study tested the hypothesis that during hypercapnia or hypoxia, airway-related vagal preganglionic neurons (AVPNs) of the nucleus ambiguus (NA) release acetylcholine (ACh), which in a paracrine fashion, activates ACh receptors expressed by inspiratory rhythm generating cells. AVPNs in the NA were ablated by injecting a saporin- (SA) cholera toxin b subunit (CTb-SA) conjugate into the extra-thoracic trachea (n=6). Control animals were injected with free CTb (n=6). In CTb treated rats, baseline ventilation and ventilatory responses to hypercapnia (5 and 12% CO(2) in O(2)) or hypoxia (8% O(2) in N(2)) were similar (p>0.05) prior to and 5 days after injection. CTb-SA injected rats maintained rhythmic breathing patterns 5 days post injection, however, tachypneic responses to hypercapnia or hypoxia were significantly reduced. The number of choline acetyltransferase (ChAT) immunoreactive cells in the NA was much lower (p<0.05) in CTb-SA rats as compared to animals receiving CTb only. These results suggest that AVPNs participate in the respiratory frequency response to hypercapnia or hypoxia.
Wu
Mingfei
M
Specialized Neuroscience Research Program, Department of Physiology and Biophysics, Howard University College of Medicine, 520 'W' Street NW, Washington, DC 20059, USA.
Kc
Prabha
P
Mack
Serdia O
SO
Haxhiu
Musa A
MA
D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002772:Cholera Toxin / Q000633:toxicity; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D008954:Models, Biological; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009407:Nerve Block / Q000379:methods; D010940:Plant Proteins / Q000633:toxicity; D012123:Pulmonary Ventilation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013909:Thorax / Q000187:drug effects / Q000294:innervation; D014132:Trachea / Q000187:drug effects / Q000294:innervation; D014630:Vagus Nerve / Q000166:cytology*
D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C420112:cholera toxin B-saporin conjugate; D002772:Cholera Toxin; D002795:Choline O-Acetyltransferase; D000076985:Saporins