Role of calcium channels in heavy metal toxicity

Cellular membranes are basically impermeable to ions and have developed specific pathways (channels, transporters or pumps) to facilitate metal translocation. These physiological carriers are not ideally selective and their specificity spectrum may include xenobiotic species, such as toxic metals whose availability in the environment has increased enormously in industrial times. I have studied the pathways of influx of two toxic metals, lead (Pb) and cadmium (Cd) in mammalian cells. Both metals interact with Ca-binding sites, but their ability to mimic Ca is different. Cd appears to permeate the cell membrane mainly through the same pathways as Ca, while Pb is also rapidly taken up in different cell types by passive transport systems that are distinct from Ca channels and independent of specific stimuli. To further elucidate the role of voltage-dependent Ca channels (VDCC) in Cd uptake, I compared the effect of this metal in two Chinese hamster ovary (CHO) cell lines, a wild type and modified cell line, which was permanently transfected with an L-type VDCC. Both cultures were subjected to brief (30-60 min) exposure to 50-100 ?M Cd in serum-free culture medium. Cell death was evident after 18-24 h with comparable features in both cell lines. Cell shrinkage, quantified by cell capacitance measurements, and metal accumulation, measured by atomic absorption spectroscopy, were also comparable in the two cell lines. However, in the permanently transfected cells, the effect of Cd treatment was partially prevented by nimodipine (VDCC antagonist) and enhanced by BayK8644 (VDCC agonist). I concluded that, although VDCC represent a pathway of Cd entry and participate in Cd-induced toxicity, as demonstrate by the effect of dihydropyridine (DHP) modifiers, expression of L-type Ca channels is not sufficient to modify Cd accumulation and sensitivity to a toxicological significant extent. Thus both Cd and Pb can take advantage of VDCC to permeate the membrane, but these transport proteins are not the only, and frequently not the most important, pathways of permeation