Exploring the Potential Roles of Band 3 and Aquaporin-1 in Blood CO2 Transport–Inspired by Comparative Studies of Glycophorin B-A-B Hybrid Protein GP.Mur

Abstract

The Cl—/HCO3— exchanger band 3 is functionally relevant to blood CO2 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 HCO3—/CO2 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 CO2 respiration. The second part of the review explores the transport of water, which is the other substrate for intra-erythrocytic CO2/HCO3— conversion (an essential step in blood CO2 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 CO2 transport. Research in this area is complicated by the fact that the H2O/CO2-transporting function of AQP1 is replaceable by other erythrocyte channels/transporters (e.g., UT-B/GLUT1 for H2O; RhAG for CO2). Recently, using carbonic anhydrase II (CAII)-filled erythrocyte vesicles, AQP1 has been demonstrated to transport water for the CAII-mediated reaction, CO2(g) + H2O ⇌ HCO3—(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, CO2-transport metabolon (AQP1, band 3, CAII and deoxygenated hemoglobin). Their dynamic interaction is envisioned to facilitate blood CO2 respiration, in the presence of constantly changing osmotic and hemodynamic stresses during circulation.

AQP1 (aquaporin 1 (Colton blood group))

“…The CO2-transporting function of APQ1 is replaceable by RHAG gas channel. (Hsu 2018). AQP1 is expressed in all tissues, in particular in renal tubules, exocrine pancreas, neuropil (synaptically dense regions of brain), bile ducts, corneal endothelium, bone marrow, myoepithelial cells of breast and endothelial cells (The Human Protein Atlas).…”

“…There are 160,000-200,000 copies of AQP1 on one erythrocyte membrane (Hsu 2018). AQP1 forms complex with SLC4A1 (band 3) and CA2 (carbonic anhydrase II) for intraerythrocytic CO2/HCO3 conversion in relation to desoxy-hemoglobin (Hsu 2018). 60% of CO2 flux in or out of RBCs is via AQP1 gas channel.…”

“…60% of CO2 flux in or out of RBCs is via AQP1 gas channel. The rest of CO2 flux is likely through another gas channel, RHAG, and/or direct diffusion (Hsu 2018).…”

Comodulation of NO-Dependent Vasodilation by Erythroid Band 3 and Hemoglobin: A GP.Mur Athlete Study

“…The structural-functional hallmarks of GP.Mur+ red cells are enhanced band 3 expression (18) and altered band 3 complex structure with other membrane proteins on the red cell surface (21,(24)(25)(26). GP.Mur+ red cells present stronger band 3-AQP1 interaction (18,26), contain reduced amount of RhAG and consequently altered band 3-Rh/RhAG macrocomplex organization (25,27), and are more resilient physically in the osmolarity-fragility test (18).…”

An Insight into the Stages of Ion Leakage during Red Blood Cell Storage

“…It is dependent of extracellular saline, whose increased concentration promotes more pronounced flux of Na + and K + [ 16 , 17 ]. The protein responsible for the regulation of the levels of Cl − and HCO 3 − is called capnophorin, also known as band 3 [ 18 ]. Band 3 covers approximately 26% of the membrane surface [ 19 ] and performs chloride shift, which is crucial for gas exchange.…”