Regulation of erythrocyte function: Multiple evolutionary solutions for respiratory gas transport and its regulation...

Gas transport concepts in vertebrates have naturally been formulated based on human blood. However, the first vertebrates were aquatic, and fish and tetrapods diverged hundreds of millions years ago. Water-breathing vertebrates live in an environment with low and variable O₂ levels, making environmental O₂ an important evolutionary selection pressure in fishes, and various features of their gas transport differ from humans. Erythrocyte function in fish is of current interest, because current environmental changes affect gas transport, and because especially zebrafish is used as a model in biomedical studies, making it important to understand the differences in gas transport between fish and mammals to be able to carry out meaningful studies. Of the close to thirty thousand fish species, teleosts are the most species-numerous group. However, two additional radiations are discussed: agnathans and elasmobranchs. The gas transport by elasmobranchs may be closest to the ancestors of tetrapods. The major difference in their haemoglobin (Hb) function to humans is their high urea tolerance. Agnathans differ from other vertebrates by having Hbs, where cooperativity is achieved by monomer-oligomer equilibria. Their erythrocytes also lack the anion exchange pathway with profound effects on CO₂ transport. Teleosts are characterized by highly pH sensitive Hbs, which can fail to become fully O₂ -saturated at low pH. An adrenergically stimulated Na⁺ /H⁺ exchanger has evolved in their erythrocyte membrane, and plasma-accessible carbonic anhydrase can be differentially distributed among their tissues. Together, and differing from other vertebrates, these features can maximize O₂ unloading in muscle while ensuring O₂ loading in gills.