Cadmium inhibition of the erythrocyte Ca2+ pump. A molecular interpretation

The effects of cadmium (Cd2+) on transmembrane Ca2+ transport and on the membrane permeability for Ca2+ were studied in human erythrocytes. The erythrocyte Ca2+ pump is inhibited competitively by Cd2+ via interaction with the Ca2+ transport site of the carrier and not via interaction with its activator calmodulin. The affinity of the Ca2+ pump for Cd2+ is extremely high (KI = 2.0 nM Cd2+). Cd2+ (less than or equal to 10(-4) M) does not alter the membrane permeability for Ca2+. We conclude that the pivotal mechanism in the toxic action of Cd2+ is the inhibition of Ca2+-ATPase mediated Ca2+ extrusion. As a result Cd2+ disturbs intracellular Ca2+ homeostasis and may increase cytosolic Ca2+ (Ca2+i) to toxic levels.