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.
Verbost
P M
PM
Department of Animal Physiology, Faculty of Science, Nijmegen, The Netherlands.
Flik
G
G
Pang
P K
PK
Lock
R A
RA
Wendelaar Bonga
S E
SE
D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000097:blood*; D004910:Erythrocyte Membrane / Q000201:enzymology*; D006801:Humans; D007700:Kinetics
D002104:Cadmium; D000252:Calcium-Transporting ATPases; D002118:Calcium