EFFECT OF CADMIUM ON CALCIUM-TRANSPORT IN A HUMAN FETAL HEPATIC CELL-LINE (WRL-68 CELLS)

Toxic metals appear to use the transport pathways that exist for biolo gically essential metals, Calcium uptake in cells occurs through speci fic membrane channels. Since cadmium inhibits calcium uptake, this stu dy was carried on to elucidate the mechanism of Cd interference with c alcium transport using the fetal hepatic cell line WRL-68 as an in vit ro model. Ca accumulation by WRL-68 cells presented an initial rapid p hase, Followed by a sustained phase of slower accumulation over a 60 m in period. A concentration of 50 mu M CdCl2 produced 39% inhibition of the uptake of CaCl2 (100 mu M), while 100 mu M nifedipine or verapami l decreased Ca accumulation by 35 and 63%, respectively. All Cd concen trations tested produced significant decrease in Ca uptake in a concen tration-dependent manner at 1 min and thereafter, although with 10 mu M CdCl2 no significant difference was found after 30 min of incubation .-From the Lineweaver-Burk plot, we found that Cd exerted a competitiv e inhibition on Ca uptake, since there was no significant effect on th e V-max but an increased K-m. A second order rate constant of Cd inact ivation of 0.061 mM(-1). s(-1) was determined from the course of Ca up take during Cd inhibition. SH groups seemed to play an essential role in Ca inhibition uptake by Cd because the inhibition of Ca accumulatio n by 50 mu M Cd was practically reversed after the addition of dithiot hreitol.