A novel perspective on the evolutionary loss of plasma-accessible carbonic anhydrase at the teleost gill

The gills of most teleost fishes lack plasma-accessible carbonic anhydrase (paCA) that could participate in CO(2) excretion. We tested the prevailing hypothesis that paCA would interfere with red blood cell (RBC) intracellular pH regulation by β-adrenergic sodium-proton exchangers (β-NHE) that protect pH-sensitive haemoglobin–oxygen (Hb–O(2)) binding during an acidosis. In an open system that mimics the gills, β-NHE activity increased Hb–O(2) saturation during a respiratory acidosis in the presence or absence of paCA, whereas the effect was abolished by NHE inhibition. However, in a closed system that mimics the tissue capillaries, paCA disrupted the protective effects of β-NHE activity on Hb–O(2) binding. The gills are an open system, where CO(2) generated by paCA can diffuse out and is not available to acidifying the RBCs. Therefore, branchial paCA in teleosts may not interfere with RBC pH regulation by β-NHEs, and other explanations for the evolutionary loss of the enzyme must be considered.