Exploring the Potential Roles of Band 3 and Aquaporin-1 in Blood CO 2 Transport-Inspired by Comparative Studies of Glycophorin B-A-B Hybrid Protein GP.Mur.

The Cl ^- /HCO ₃ ^- exchanger band 3 is functionally relevant to blood CO ₂ transport. Band 3 is the most abundant membrane protein in human red blood cells (RBCs). Our understanding of its physiological functions mainly came from clinical cases associated with band 3 mutations. Severe reduction in band 3 expression affects blood HCO ₃ ^- /CO ₂ metabolism. What could happen physiologically if band 3 expression is elevated instead? In some areas of Southeast Asia, about 1-10% of the populations express GP.Mur, a glycophorin B-A-B hybrid membrane protein important in the field of transfusion medicine. GP.Mur functions to promote band 3 expression, and GP.Mur red cells can be deemed as a naturally occurred model for higher band 3 expression. This review first compares the functional consequences of band 3 at different levels, and suggests a critical role of band 3 in postnatal CO ₂ respiration. The second part of the review explores the transport of water, which is the other substrate for intra-erythrocytic CO ₂ /HCO ₃ ^- conversion (an essential step in blood CO ₂ transport). Despite that water is considered unlimited physiologically, it is unclear whether water channel aquaporin-1 (AQP1) abundantly expressed in RBCs is functionally involved in CO ₂ transport. Research in this area is complicated by the fact that the H ₂ O/CO ₂ -transporting function of AQP1 is replaceable by other erythrocyte channels/transporters (e.g., UT-B/GLUT1 for H ₂ O; RhAG for CO ₂ ). Recently, using carbonic anhydrase II (CAII)-filled erythrocyte vesicles, AQP1 has been demonstrated to transport water for the CAII-mediated reaction, CO _2(g) + H ₂ O ⇌ HCO ₃ ^- _(aq) + H ⁺ _(aq) . AQP1 is structurally associated with some population of band 3 complexes on the erythrocyte membrane in an osmotically responsive fashion. The current findings reveal transient interaction among components within the band 3-central, CO ₂ -transport metabolon (AQP1, band 3, CAII and deoxygenated hemoglobin). Their dynamic interaction is envisioned to facilitate blood CO ₂ respiration, in the presence of constantly changing osmotic and hemodynamic stresses during circulation.