The Interaction between (Ca2++ Mg2+)-ATPase and the Soluble Activator (Calmodulin) in Erythrocytes Containing Haemoglobin S

Abstract

In normal human erythrocytes, a membrane-bound (Ca2+ + Mg2+)-ATPase is stimulated by a soluble activator, calmodulin. Since cells containing Hb S accumulate excessive Ca2+, the defect could lie in either the (Ca2+ + Mg2+)-ATPase or calmodulin. To decide between these 2 possibilities, (Ca2+ + Mg2+)-ATPase was prepared from erythrocytes of normal (AA), sickle cell trait (AS) and sickle cell disease (SS) individuals. Calmodulin was prepared from hemolysates from AA and SS erythrocytes. The enzyme prepared from SS ghosts had lower specific activity than that from AA membranes. Calmodulin from either source did not stimulate the ATPase of SS erythrocytes. Enzyme from AS cells had specific activity similar to that of enzyme prepared from SS membranes. The enzymatic activity of a mixed cell population obtained from an SS patient 8 days following exchange transfusion was proportional to the percent Hb A. Calmodulin apparently is unable to interact with the enzyme site on the SS membrane. This inability could be due to a specific property of the membrane and not an abnormality of calmodulin itself.