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(The FASEB Journal. 2006;20:1974-1981.)
© 2006 FASEB

Evidence that aquaporin 1 is a major pathway for CO2 transport across the human erythrocyte membrane

V. Endeward, R. Musa-Aziz*, G. J. Cooper*,1, L.-M. Chen*, M. F. Pelletier*, L. V. Virkki*,2, C. T. Supuran{dagger}, L. S. King{ddagger}, W. F. Boron* and G. Gros3

Zentrum Physiologie, Abt. Vegetative Physiologie, Medizinische Hochschule Hannover, Hannover, Germany;
* Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut, USA;

{dagger} Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, University of Florence, Sesto Fiorentino, Firenze, Italy; and

{ddagger} Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA

3Correspondence: Zentrum Physiologie, Abt. Vegetative Physiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany. E-mail: gros.gerolf{at}mh-hannover.de

We report here the application of a previously described method to directly determine the CO2 permeability (PCO2) of the cell membranes of normal human red blood cells (RBCs) vs. those deficient in aquaporin 1 (AQP1), as well as AQP1-expressing Xenopus laevis oocytes. This method measures the exchange of 18O between CO2, HCO3, and H2O in cell suspensions. In addition, we measure the alkaline surface pH (pHS) transients caused by the dominant effect of entry of CO2 vs. HCO3 into oocytes exposed to step increases in [CO2]. We report that 1) AQP1 constitutes the major pathway for molecular CO2 in human RBCs; lack of AQP1 reduces PCO2 from the normal value of 0.15 ± 0.08 (SD; n=85) cm/s by 60% to 0.06 cm/s. Expression of AQP1 in oocytes increases PCO2 2-fold and doubles the alkaline pHS gradient. 2) pCMBS, an inhibitor of the AQP1 water channel, reduces PCO2 of RBCs solely by action on AQP1 as it has no effect in AQP1-deficient RBCs. 3) PCO2 determinations of RBCs and pHS measurements of oocytes indicate that DIDS inhibits the CO2 pathway of AQP1 by half. 4) RBCs have at least one other DIDS-sensitive pathway for CO2. We conclude that AQP1 is responsible for 60% of the high PCO2 of red cells and that another, so far unidentified, CO2 pathway is present in this membrane that may account for at least 30% of total PCO2.—Endeward, V., Musa-Aziz, R., Cooper, G. J., Chen, L., Pelletier, M. F., Virkki, L. V., Supuran, C. T., King, L. S., Boron, W. F., Gros, G. Evidence that aquaporin 1 is a major pathway for CO2 transport across the human erythrocyte membrane.


Key Words: human red cell membrane • CO2 permeability • pCMBS • DIDS




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