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 CO(2) diffusivity, and it has been proposed that they may serve as transmembrane channels for CO(2) 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 CO(2) elimination by the lung. To test whether these membrane proteins contribute to CO(2) elimination in vivo, we measured CO(2) exchange in buffer- and blood-perfused rabbit lungs before and after addition of 0.5 mM ZnCl(2), an inhibitor of both AQ-mediated CO(2) diffusion and voltage-gated H(+) channels. For comparison, red cell and lung carbonic anhydrases (CAs) were inhibited by 0.1 mM methazolamide. ZnCl(2) had no effect on CO(2) exchange when inspired CO(2) was altered between 2% and 5% in 5-min intervals. Pulmonary vascular and airway resistances were not altered by ZnCl(2). In contrast, methazolamide inhibited CO(2) exchange by 30% in buffer-perfused lungs and by 65% in blood-perfused lungs. Exhaled NO concentrations were unaffected by ZnCl(2) 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 CO(2) diffusion capacity by >90% to lower CO(2) 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 CO(2) elimination.
Swenson
Erik R
ER
Department of Medicine, VA Puget Sound Health Care System, University of Washington, Seattle, WA 98108, USA. eswenson@u.washington.edu
Deem
Steven
S
Kerr
Mark E
ME
Bidani
Akhil
A
D000818:Animals; D020346:Aquaporins / Q000502:physiology*; D002245:Carbon Dioxide / Q000502:physiology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000378:metabolism; D008704:Methazolamide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009924:Organ Culture Techniques; D011650:Pulmonary Alveoli / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D017967:Zinc Compounds / Q000494:pharmacology
D020346:Aquaporins; D002257:Carbonic Anhydrase Inhibitors; D002712:Chlorides; D017967:Zinc Compounds; D002245:Carbon Dioxide; D009569:Nitric Oxide; C016837:zinc chloride; D008704:Methazolamide