Bicarbonate binding to hemoglobin links oxygen and carbon dioxide transport in hagfish.

Hagfish are unusual among vertebrates in having red cells that almost completely lack the anion-exchanger membrane protein band III and hemoglobins that are highly sensitive to CO2 but only weakly affected by protons. This suggests a different linkage between oxygen and CO2 transport from that of the majority of vertebrates, which is characterized by oxygen-linked proton binding to hemoglobin and chloride-bicarbonate exchange across band III protein. We here report that the hemoglobin of the hagfish Myxtne glutinosa shows oxygen-linked binding of bicarbonate, which decreases the oxygen affinity and thereby enhances oxygen unloading to the tissues. Bicarbonate binding to the hemoglobin moreover facilitates the hydration of CO2 and its transport as intraerythrocytic bicarbonate, and may compensate at least in part for the virtual absence of band III protein. This represents a unique linkage between oxygen and CO2 transport among vertebrates, where the physiological role of protons in the Bohr and Haldane effects is played by bicarbonate ions.