Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice

• Published in: PloS one Vol. 11; no. 11; p. e0166089
• Main Authors: Reznikov, Leah R, Meyerholz, David K, Adam, Ryan J, Abou Alaiwa, Mahmoud, Jaffer, Omar, Michalski, Andrew S, Powers, Linda S, Price, Margaret P, Stoltz, David A, Welsh, Michael J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.11.2016; Public Library of Science (PLoS)
• Subjects: Acid Sensing Ion Channels - metabolism; Acidification; Acidity; Acids; Albumin; Alveoli; Animals; Arthritis; Asthma; Asthma - metabolism; Biology and Life Sciences; Biomedical engineering; Biophysics; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - chemistry; Bronchus; Depolarization; Engineering schools; Epithelium; Ganglia; Hypersensitivity; Inflammation; Inflammation - metabolism; Inflammatory response; Integrated circuits; Internal medicine; Ion channels; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Muscles; Nerve Tissue Proteins - metabolism; Nervous system; Neurons; Neuropeptides; Ovalbumin; Physicians; Physiology; Protons; Research and Analysis Methods; Respiratory Hypersensitivity - metabolism; Respiratory System - metabolism; Respiratory tract; Rodents; Sensitizing; Sensory neurons; Sensory Receptor Cells - metabolism; Smooth muscle; Social Sciences; Sodium channels; Substance P; Substance P - metabolism; Vagus nerve; Vagus Nerve - metabolism; United States > US; Iowa; Iowa City Iowa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166089

Neurons innervating the airways contribute to airway hyperreactivity (AHR), a hallmark feature of asthma. Several observations suggested that acid-sensing ion channels (ASICs), neuronal cation channels activated by protons, might contribute to AHR. For example, ASICs are found in vagal sensory neurons that innervate airways, and asthmatic airways can become acidic. Moreover, airway acidification activates ASIC currents and depolarizes neurons innervating airways. We found ASIC1a protein in vagal ganglia neurons, but not airway epithelium or smooth muscle. We induced AHR by sensitizing mice to ovalbumin and found that ASIC1a-/- mice failed to exhibit AHR despite a robust inflammatory response. Loss of ASIC1a also decreased bronchoalveolar lavage fluid levels of substance P, a sensory neuropeptide secreted from vagal sensory neurons that contributes to AHR. These findings suggest that ASIC1a is an important mediator of AHR and raise the possibility that inhibiting ASIC channels might be beneficial in asthma.