Elevated Erythrocyte Calcium in Sickle Cell Disease

Abstract

CUMULATIVE membrane damage and loss is thought to occur in the erythrocytes of individuals homozygous for haemoglobin S (refs 1–4). The culmination of this process seems to be the formation of irreversibly sickled cells (ISC), which will not resume normal biconcave disk shape, even when the haemoglobin which they contain is in the sol (oxygenated) state^5–7. Although the processes responsible for the formation of ISC have not yet been fully elucidated, it is clear that a change in the structure or composition of the membrane has occurred, such that cellular plasticity and ability to resume normal shape upon oxygenation have been lost. Weed et al.⁸ report a similar loss of plasticity, a diminished ease of ingress into glass microcapillaries, when calcium is placed inside resealed membrane “ghosts” made from normal human erythrocytes. In whole red cells, diminished filterability was also found to occur concomitantly with progressive loss of ATP. ATP-depleted red cells, however, retained most of their plasticity if EDTA were added to the incubation mixture to prevent calcium accumulation⁸. These results indicate that increased calcium alone may markedly reduce red cell plasticity.