Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.

Summary Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation. Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na + transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Cl − secretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinhi-A01. Decreased mRNA expression of α, β, and γ ENaC, and increased mRNA expression of the CaCC transmembrane member 16A, distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation.Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na + transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Clsecretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinh-A01. Decreased mRNA expression of a, b, and g ENaC, and increased mRNA expression of the CaCC transmembrane member 16A distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

Hypertonic solutions increase airway surface liquid (ASL) through cholinergically‐mediated epithelial cell ion transport and osmosis. Thus, mammals inhabiting salt marshes might have acquired adaptations, including greater dependence upon cholinergic mechanisms, for ASL regulation. To test this hypothesis, we investigated the airways of the rice rat, a medium‐sized rodent that inhabits salt marshes. We discovered unique ion transport properties, including minimal amiloride‐sensitive Na+ absorption and limited Cl− secretion through the cystic fibrosis transmembrane conductance regulator. In contrast, the cholinergic agonist carbachol induced a large Cl− secretory current that was blocked by the calcium‐activated chloride channel inhibitor CaCCinh‐A01. Rice rat airway cultures also secreted fluid in response to carbachol, and when challenged with 3.5% NaCl apically to mimic exposure to sea water aerosols, displayed a prolonged expansion of the ASL volume. These data suggest that the rice rat airway might possess unique ion transport mechanisms to facilitate survival in the harsh salt marsh environment.Support or Funding InformationHL119560, 0T2TR001983, DE0237863This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.