Cadmium inhibits plasma membrane calcium transport.
The interaction of Cd2+ with the plasma membrane Ca2+-transporting ATPase of fish gills was studied. ATP-driven Ca2+-transport in basolateral membrane (BLM) vesicles was inhibited by Cd2+ with an I50 value of 3.0 nM at 0.25 microM free Ca2+, using EGTA, HEEDTA and NTA to buffer Ca2+ and Cd2+ concentrations. The inhibition was competitive in nature since the K0.5 value for Ca2+ increased linearly with increasing Cd2+ concentrations while the Vmax remained unchanged. The Ca2+ pump appeared to be calmodulin dependent, but we conclude that the inhibition by Cd2+ occurs directly on the Ca2+-binding site of the Ca2+-transporting ATPase and not via the Ca2+-binding sites of calmodulin. It is suggested that Cd2+-induced inhibition of Ca2+-transporting enzymes is the primary effect in the Cd2+ toxicity towards cells followed by several secondary effects due to a disturbed cellular Ca2+ metabolism. Our data illustrate that apparent stimulatory effects of low concentrations of Cd2+ on Ca2+-dependent enzymes may derive from increased free-Ca2+ levels when Cd2+ supersedes Ca2+ on the ligands.
Department of Animal Physiology, Faculty of Science, University of Nijmegen, The Netherlands.
P M
PM
Verbost
G
G
Flik
R A
RA
Lock
S E
SE
Wendelaar Bonga
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000032:analysis / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005399:Fishes; D005880:Gills / Q000378:metabolism*; D008297:Male
D002147:Calmodulin; D002104:Cadmium; D002118:Calcium