title: Evidence against aquaporin-1-dependent CO2 permeability in lung and kidney.
abstract: AQP1-dependent CO2 transport has been suggested from the increased CO2 permeability in Xenopus oocytes expressing AQP1. Potential implications of this finding include AQP1-facilitated CO2 exchange in mammalian lung and HCO3-/CO2 transport in kidney proximal tubule. We reported previously that: (a) CO2 permeability in erythrocytes was not affected by AQP1 deletion, (b) CO2 permeability in liposomes was not affected by AQP1 reconstitution despite a 100-fold increased water permeability, and (c) CO2 blow-off by the lung in living mice was not impaired by AQP1 deletion. We extend these observations by direct measurement of CO2 permeabilities in lung and kidney. CO2 transport across the air-space-capillary barrier in isolated perfused lungs was measured from changes in air-space fluid pH in response to addition/removal of HCO3-/CO2 from the pulmonary artery perfusate. The pH was measured by pleural surface fluorescence of a pH indicator (BCECF-dextran) in the air-space fluid. Air-space fluid pH equilibrated rapidly (t(1/2) approximately 6 s) in response to addition/removal of HCO3-/CO2. However, the kinetics of pH change was not different in lungs of mice lacking AQP1, AQP5 or AQP1/AQP5 together, despite an up to 30-fold reduction in water permeability. CO2 transport across BCECF-loaded apical membrane vesicles from kidney proximal tubule was measured from the kinetics of intravesicular acidification in response to rapid mixing with a HCO3-/CO2 solution. Vesicles rapidly acidified (t(1/2) approximately 10 ms) in response to HCO3-/CO2 addition. However the acidification rate was not different in kidney vesicles from AQP1-null mice despite a 20-fold reduction in water permeability. The results provide direct evidence against physiologically significant transport of CO2 by AQP1 in mammalian lung and kidney.
authors.affiliation: Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0521, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fang
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
mesh_terms: D000465:Algorithms; D000818:Animals; D051398:Aquaporin 1; D051402:Aquaporin 5; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D015824:Blood-Air Barrier / Q000502:physiology; D002196:Capillaries / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D004058:Diffusion; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009995:Osmosis; D010539:Permeability; D011650:Pulmonary Alveoli / Q000378:metabolism
chemical_list: C496021:Aqp1 protein, mouse; C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D020346:Aquaporins; D001639:Bicarbonates; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D002245:Carbon Dioxide; D051398:Aquaporin 1