Sickle red cell calcium metabolism: studies on Ca2+-Mg2+ATPase and Ca-binding properties of sickle red cell membranes.

Sickle (Hb SS) red cells, preloaded with 45Ca by reversal of hemolysis, exhibit an incomplete 45Ca extrusion, retaining approximately four times more 45Ca than normal cells. Studies indicated that neither the reduction in Hb SS cell Ca2+-Mg2+ ATPase activity (84% of normal) nor the activation of Ca2+-Mg2+ ATPase by calmodulin was sufficiently different from normal cells to attribute a major role to the calcium pump in 45Ca retention. These results suggested that 45Ca retention may reflect an alteration in the calcium-binding properties of Hb SS cell membranes. Low-affinity calcium-binding (freely dissociable) was similar in normal and Hb SS cell membranes. However, the total calcium bound with high-affinity (tightly bound) was four-to-five times greater in Hb SS cell membranes than in normal membranes. These results are compatible with the hypothesis that Hb SS cell 45Ca retention reflects an exchange of a fraction of the total 45Ca with a tightly bound calcium pool, larger in Hb SS cell membranes than in normal membranes. A comparable degree of red cell 45Ca retention, which did not correlate with the reticulocyte population, was observed in other chronic anemic states. These findings suggest that the increased high-affinity calcium binding by the membrane may be a consequence of cellular changes induced by the anemic condition.