Inhibition of aquaporin-mediated CO2 diffusion and voltage-gated H+ channels by zinc does not alter rabbit lung CO2 and NO excretion

Aquaporins (AQs) increase cell membrane CO₂ diffusivity, and it has been proposed that they may serve as transmembrane channels for CO₂ and other small gas molecules. In addition, it has been hypothesized that voltage-gated H⁺ channels located on the apical membrane of the alveolar epithelium contribute to CO₂ elimination by the lung. To test whether these membrane proteins contribute to CO₂ elimination in vivo, we measured CO₂ exchange in buffer- and blood-perfused rabbit lungs before and after addition of 0.5mM ZnCl₂, an inhibitor of both AQ-mediated CO₂ diffusion and voltage-gated H⁺ channels. For comparison, red cell and lung carbonic anhydrases (CAs) were inhibited by 0.1mM methazolamide. ZnCl₂ had no effect on CO₂ exchange when inspired CO₂ was altered between 2% and 5% in 5-min intervals. Pulmonary vascular and airway resistances were not altered by ZnCl₂. In contrast, methazolamide inhibited CO₂ exchange by 30% in buffer-perfused lungs and by 65% in blood-perfused lungs. Exhaled NO concentrations were unaffected by ZnCl₂ or by CA inhibition. Lung capillary gas exchange modelling shows that under normal resting conditions it would be necessary to reduce the alveolar–capillary membrane CO₂ diffusion capacity by >90% to lower CO₂ elimination by 10%. Therefore we conclude that red cell and lung AQs and voltage-gated H⁺ channels in the alveolar epithelium contribute minimally to normal physiological CO₂ elimination.