Cytotoxicity of cadmium and characteristics of its transport in cardiomyocytes

Cadmium (Cd) is reported to produce cardiotoxicity at doses and exposure co nditions that cause no effect in kidney or liver. The purpose of the presen t investigation was to examine the cytotoxicity of Cd to neonatal rat cardi omyocytes in primary culture and to elucidate the transport characteristics of Cd in these cells at a non-toxic concentration. Cd concentrations of 0. 1 mu M and higher that are well tolerated by hepatocytes and renal cortical epithelial cells were toxic to the cardiomyocyte. The plot of initial upta ke rate of Cd at various concentrations was nonlinear suggesting that, in a ddition to simple diffusion, other processes may also be involved. These pr ocesses required metabolic energy as pretreatment with dinitrophenol or sod ium fluoride inhibited 58 and 59% of the Cd uptake, respectively. The uptak e of Cd was also affected by the incubation temperature and lowering the te mperature from 37 to 4 degrees C reduced Cd uptake over 30 min by 61%. Cd u ptake required interaction with membrane sulfhydryl groups; pretreatment wi th p-chloromercuribenzenesulfonic acid or mercuric chloride reduced Cd upta ke by 46 and 58%, respectively. Cd utilized the transport pathways for calc ium (Ca), zinc (Zn), and copper (Cu). Coincubation with 1.26 mM Ca competit ively inhibited Cd uptake by 77%. In the presence of Ca, 30 mu M Zn or Cu f urther inhibited Cd accumulation competitively by as much as 63 and 32%, re spectively. Cd could enter the cardiomyocytes through Ca channels and Ca ch annel blocker, verapamil, inhibited up to 76% of Cd uptake. From the above results it can be concluded that Cd is highly toxic to the cardiomyocytes. A majority of Cd enters these cells through transport processes that exist for Ca, Zn, and Cu. The transport processes utilized by Cd are temperature sensitive and dependent on metabolic energy. Furthermore, these involve mem brane sulfhydryl groups and include Ca channels. (C) 1999 Academic Press.