title: Cadmium inhibition of the erythrocyte Ca2+ pump. A molecular interpretation.
abstract: 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.
authors.affiliation: Department of Animal Physiology, Faculty of Science, Nijmegen, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Verbost
authors.forename: G
authors.initials: G
authors.lastname: Flik
authors.forename: P K
authors.initials: PK
authors.lastname: Pang
authors.forename: R A
authors.initials: RA
authors.lastname: Lock
authors.forename: S E
authors.initials: SE
authors.lastname: Wendelaar Bonga
mesh_terms: 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
chemical_list: D002104:Cadmium; D000252:Calcium-Transporting ATPases; D002118:Calcium