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

摘要

The airway‐surface liquid pH (pH ASL ) is slightly acidic relative to the plasma and becomes more acidic in airway diseases, leading to impaired host defense. CO 2 in the large airways decreases during inspiration (0.04% CO 2 ) and increases during expiration (5% CO 2 ). Thus, we hypothesized that pH ASL would fluctuate during the respiratory cycle. We measured pH ASL on cultures of airway epithelia while changing apical CO 2 concentrations. Changing apical CO 2 produced only very slow pH ASL 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 2 ‐induced pH ASL changes. In contrast, adding carbonic anhydrase significantly increased the rate of change in pH ASL . Using pH‐dependent rates obtained from these experiments, we modeled the pH ASL during respiration to further understand how pH changes with physiologic and pathophysiologic respiratory cycles. Modeled pH ASL oscillations were small and affected by the respiration rate, but not the inspiratory:expiratory ratio. Modeled equilibrium pH ASL 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 2 fluctuations. We speculate that the airways may have evolved minimal carbonic anhydrase activity to mitigate large changes in the pH ASL during breathing that could potentially affect pH‐sensitive components of ASL.