Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes during breathing

Ian M Thornell; Xiaopeng Li; Xiao Xiao Tang; Christian M Brommel; Philip H Karp; Michael J Welsh; Joseph Zabner

doi:10.14814/phy2.13569

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Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes during breathing

Journal article

Open access

Peer reviewed

Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes during breathing

Ian M Thornell, Xiaopeng Li, Xiao Xiao Tang, Christian M Brommel, Philip H Karp, Michael J Welsh and Joseph Zabner

Physiological reports, Vol.6(2), pp.e13569-n/a

01/2018

DOI: 10.14814/phy2.13569

PMCID: PMC5789725

PMID: 29380953

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Abstract

The airway-surface liquid pH (pH ) is slightly acidic relative to the plasma and becomes more acidic in airway diseases, leading to impaired host defense. CO in the large airways decreases during inspiration (0.04% CO ) and increases during expiration (5% CO ). Thus, we hypothesized that pH would fluctuate during the respiratory cycle. We measured pH on cultures of airway epithelia while changing apical CO concentrations. Changing apical CO produced only very slow pH changes, occurring in minutes, inconsistent with respiratory phases that occur in a few seconds. We hypothesized that pH changes were slow because airway-surface liquid has little carbonic anhydrase activity. To test this hypothesis, we applied the carbonic anhydrase inhibitor acetazolamide and found minimal effects on CO -induced pH changes. In contrast, adding carbonic anhydrase significantly increased the rate of change in pH . Using pH-dependent rates obtained from these experiments, we modeled the pH during respiration to further understand how pH changes with physiologic and pathophysiologic respiratory cycles. Modeled pH oscillations were small and affected by the respiration rate, but not the inspiratory:expiratory ratio. Modeled equilibrium pH was affected by the inspiratory:expiratory ratio, but not the respiration rate. The airway epithelium is the only tissue that is exposed to large and rapid CO fluctuations. We speculate that the airways may have evolved minimal carbonic anhydrase activity to mitigate large changes in the pH during breathing that could potentially affect pH-sensitive components of ASL.

Animals, Newborn

Animals

Respiratory Mucosa - chemistry

Swine

Respiratory Mucosa - enzymology

Respiration

Carbonic Anhydrases - metabolism

Hydrogen-Ion Concentration

Details

Title: Subtitle: Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes during breathing
Creators: Ian M Thornell - Howard Hughes Medical Institute, University of Iowa, Iowa City, IA
Xiaopeng Li - Department of Internal Medicine, University of Iowa, Iowa City, IA
Xiao Xiao Tang - Howard Hughes Medical Institute, University of Iowa, Iowa City, IA
Christian M Brommel - Department of Internal Medicine, University of Iowa, Iowa City, IA
Philip H Karp - Howard Hughes Medical Institute, University of Iowa, Iowa City, IA
Michael J Welsh - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA
Joseph Zabner - Department of Internal Medicine, University of Iowa, Iowa City, IA
Resource Type: Journal article
Publication Details: Physiological reports, Vol.6(2), pp.e13569-n/a
DOI: 10.14814/phy2.13569
PMID: 29380953
PMCID: PMC5789725
NLM abbreviation: Physiol Rep
eISSN: 2051-817X
Grant note: P30 ES005605 / NIEHS NIH HHS P01 HL091842 / NHLBI NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 01/2018
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984094388902771

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