Red blood cell Na pump: Insights from species differences

The red blood cell membrane is specialized to exchange chloride and bicarbonate; usually the pH gradient, the chloride ratio, and the membrane potential are tightly coupled. We review the evidence that led to the ability to separately vary inside and outside pH in red cells. The effect of pH on Na pump activity and on the selectivity of the inside and the outside transport sites is reviewed. In red blood cells, at high pH, the outside site is not selective. An increase in protons leads to an increase in K+ affinity, thus making the site more selective. The pK for this site is different in rats and humans; because of the high conservation of residues in these two species, there are only a few possible residues that can account for this difference. On the inside, work from unsided preparations suggests that, at high pH, the transport site is highly selective for Na+. Once again, an increase in protons leads to an increase in K+ affinity, but now the result is a less selective site. During their maturation, reticulocytes lose many membrane proteins. The type and fractional loss is species dependent. For example, most reticulocytes lose most of their Na pumps, retaining about 100 pumps per cell, but animals from the order Carnivora lose all their pumps. We review some of the evidence that PKC phosphorylation of N-terminus serines is responsible for endocytosis in other cell types and species variation in this region.