Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice.
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.
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Leah R
LR
Reznikov
Department of Pathology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
David K
DK
Meyerholz
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa, United States of America.
Ryan J
RJ
Adam
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Mahmoud
M
Abou Alaiwa
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Omar
O
Jaffer
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Andrew S
AS
Michalski
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Linda S
LS
Powers
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Margaret P
MP
Price
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Department of Molecular Physiology and Biophysics, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, Iowa, United States of America.
David A
DA
Stoltz
Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Department of Molecular Physiology and Biophysics, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Pappajohn Biomedical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.|Howard Hughes Medical Institute, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Michael J
MJ
Welsh
D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism
C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D013373:Substance P