In sharp contrast to these genetically
In sharp contrast to these genetically altered animals, there are two types of living fish that appear to lack Band 3 in their red blood cells. These are the Lamprey  and the Hagfish [46,47]. While these fish normally occupy their respective niches, the presumed compensatory mechanisms, as with the mice and cows, that provide for their normal activity, have yet to be delineated.
Red blood CCT241533 of unusual size and shape It is not clear how familiar the red cell community is with the 1875 paper of Gulliver  in which he presents an impressive diagram (Plate LV) of the variation in the size and shape of red blood cells across the vertebrate phyla. Sizes range from a few μm (e.g. sheep and goats) to more than 60 μm (Amphiuma and Lungfish). While Amphiuma (a salamander) is perhaps the largest, there are six species of lungfish that also have giant red blood cells. These are: one in Australia (Neocerato-dontidae), one in South America (Lepidosirenidae) and four in Africa (all Protopteridaes). The diagram of Gulliver shows red cells from the Siren, the Lepidosiren, the Sieboldia and the Proteus lungfish. All of these species breath air and have special and very interesting adaptations to their respective environments, which the reader can pursue separately (, pp. 40–41). Mention should also be made of different groups of salamanders in the family plethodontids that have lost their nuclei. One example is given by the Batrachosep species, attenuatus, in which more than 99% of the cells are enucleated . These authors make the interesting suggestion that enucleation which results in smaller cells provides for an increase in cell number and perhaps an increase in O2 capacity. Whether this explanation represents a rationale for mammalian red cells, all of which are enucleated, is an open question. It is really curious that there is a remarkable correlation between DNA content of vertebrate red cells and their cell volume [51,52]. This is illustrated in Fig. 2, which shows DNA contents for cells from different vertebrates and the graph of Fig. 3, indicates the relationship of the different cell contents of DNA to cell volume. There is as yet no explanation for why this relationship exists . A final consideration concerns red blood cells that have elliptical shapes. The normal constituents of all of the camelidae species mentioned earlier have only red cell shaped elliptocytes circulating in their bloods. It may be that some of the camels' circulating red cells also contain marginal bands which is evidently unique among mammals  although they are normally found in the red cells of most if not all of the other vertebrates . The marginal bands in camel red cells, to the extent they occur, evidently appear mainly during their maturation. Even so it is not clear what their function is or if they contribute to the stability or structure of the cell. Certain humans also have hereditary elliptocytosis, which is considered a disease . Their elliptocytic cells do not contain marginal bands. It is of course interesting that the ghosts of human elliptocytes are also elliptical  and raises questions concerning the membrane/cytoskeleton structure that is responsible for their cell shape. An important and recurring question surrounds how and where the shape transition from reticulocyte to mature elliptocyte occurs. A possible future article may include studies on the flicker phenomenon of red cells, the use and results with molecular tweezer techniques, Rouleaux formation, the process of ghost membrane resealing with temperature following hemolysis, ATP release, pump compartmentation and the remarkable process of red cell tank-treading that occurs when the cells are exposed to shear stress.
Introduction Erythrocytes of patients with sickle cell disease (SCD) exhibit increased activity of K+ leak pathways. The resulting cell shrinkage produces a population of dense cells with elevated intracellular concentrations of HbS. When these dense, dehydrated erythrocytes are deoxygenated, the lagtime for the onset of deoxyHbS polymerization is accelerated, increasing risk of endothelial adhesion and vaso-occlusion . Increased proportions of dense, dehydrated erythrocytes are associated with increased incidence of severe SCD manifestations such as skin ulcer, priapism, and renal dysfunction, and with indices of hemolysis such as elevated serum bilirubin and lactate dehydrogenase . Major K+ leak pathways promoting increased dehydration of human sickle cells include the Gardos channel Kcnn4 and the Na+-independent K–Cl cotransporters. Pharmacological blockade of these leak pathways remains a therapeutic goal for the adjunct treatment of SCD , , , envisioned as combination therapy with inducers of HbF , ,  and likely also with blockers of sickle cell adhesion to activated endothelial cells . The Kcnn4 blocker senicapoc , a congener of the antifungal Kcnn4 blocker clotrimazole , has been shown to reduce the proportion of densest erythrocytes, increase mean corpuscular volume, decrease intracellular HbS concentration, improve anemia, and decrease indices of hemolysis , . Blockers of K–Cl cotransport suitable for clinical use are actively being sought , but are not currently available.