Across species: A comparative perspective on red cell homeostasis and its influence on our understanding of human physiology and disease.

This review emphasises how studies on animal red cells have enriched our understanding of the behaviour of those from humans. For example, the pump-leak model for long-term volume stability is indebted to work on high potassium (HK)- and low potassium (LK)-containing sheep red cells. Studies in several species including trout have been useful for detailing how the co-ordinated behaviour of red cell transport proteins is involved in shorter term volume homeostasis and other functions. Our understanding of how protein phosphorylation pathways control the activity of the cation-chloride cotransporters has been given impetus by work in rabbit, sheep, trout and other species. Red cells from dogs and cats were historically important for developing theories on macromolecular crowding and cation permeability. Cattle red cells have helped substantiate that band 3 is not essential for red cell integrity. Work in many other species has informed our understanding of red cell physiology and a discussion of these areas illustrates how a comparative perspective has resoundingly enhanced and enriched our knowledge of human red cell physiology. A similar comparative approach to red cell pathophysiology is much less comprehensive although it has the potential to be invaluable for a better understanding of problems in humans.