Journal article
Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice
PloS one, Vol.11(11), pp.e0166089-e0166089
2016
DOI: 10.1371/journal.pone.0166089
PMCID: PMC5098826
PMID: 27820848
Abstract
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.
Details
- Title: Subtitle
- Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice
- Creators
- Leah R Reznikov - Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaDavid K Meyerholz - Department of Pathology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaRyan J Adam - Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa, United States of AmericaMahmoud Abou Alaiwa - Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaOmar Jaffer - Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaAndrew S Michalski - Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaLinda S Powers - Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaMargaret P Price - Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaDavid A Stoltz - Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa, United States of AmericaMichael J Welsh - Howard Hughes Medical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(11), pp.e0166089-e0166089
- DOI
- 10.1371/journal.pone.0166089
- PMID
- 27820848
- PMCID
- PMC5098826
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS T32 HL007638 / NHLBI NIH HHS K99 HL119560 / NHLBI NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pathology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984083281002771
Metrics
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