Carbonic anhydrase (CA) functions to accelerate the reaction CO 2 (g) + H 2 O ⇌ HCO 3 - (aq) + H + (aq) bidirectionally. The major functional type of CA (CAII) primarily resides inside the red blood cells (RBCs) and interacts with anion exchanger-1 (AE1). AE1 determines HCO 3 - permeability across the RBC membrane, and is the rate-limiting factor for intraerythrocytic CO 2 (g)/HCO 3 - (aq) conversion. To explore how acetazolamide, a potent CA inhibitor, could affect AE1-CAII function in respiration, we utilized a glycophorin B-A-B variant GPMur knock-in mouse model characteristic of higher erythroid AE1 expression for whole-body plethysmography (WBP). We found that acetazolamide influenced WBP respiratory parameters in the same direction as hypercapnia stimulation. Importantly, GPMur/higher AE1 increased respiratory sensitivity to acetazolamide. The findings also verify that AE1 and CAII function in concert for intraerythrocytic CO 2 /HCO 3 - conversion. Future work should address whether acetazolamide dosage shall be reduced for people bearing the GP.Mur blood type. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Kate Hsu (2026) studied this question.