Role of Calcium Channels in Heavy Metal Toxicity

Abstract

The role of voltage-dependent Ca channels (VDCC) in the membrane permeation of two toxic metals, lead (Pb) and cadmium (Cd), was studied in mammalian cells. Both metals interact with Ca-binding sites, but, while Cd influx appears to occur mainly through the same pathways as Ca, Pb is also rapidly taken up by different passive transport systems. Furthermore, I compared the effect of Cd in two Chinese hamster ovary (CHO) cell lines, a wild-type and a modified cell line, which were permanently transfected with an L-type VDCC. When cultures were subjected to a brief (30–60 min) exposure to 50–100 μM Cd, apoptotic features, metal accumulation, and death were comparable in both cell lines although, in transfected cells, the effect of Cd treatment was partially prevented by nimodipine (VDCC antagonist) and enhanced by BayK8644 (VDCC agonist). Thus, expression of L-type Ca channels is not sufficient to modify Cd accumulation and sensitivity to a toxicological significant extent and while both Cd and Pb can take advantage of VDCC to permeate the membrane, these transport proteins are not the only, and frequently not the most important, pathways of permeation.

Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels

“…The properties of Pb 2+ on other Ca 2+− dependent receptors and transporters are likely implicated by our data. Although the IC50 values are somewhat higher for Cav1.2 channels in neurons and in HEK293 cells (~1.5 μM) compared to those found here for isolated cardiomyocytes, a likely explanation is that the dose-response curves from the former were determined using Ba 2+ not Ca 2+ in the supporting solutions (Marchetti 2013). The affinity of Ba 2+ for the ion permeation pathway and selectivity filter of Cav1.2 channels is less than for Ca 2+ (Li et al 2010).…”

A Model of Cadmium Uptake and Transport in Caco-2 Cells

“…Transporter DMT1 is responsible for the first phase (u 1 , k 1 ) of cadmium accumulation in the cell [3]; it is saturable, but the mechanism of its inactivation by cadmium ions is not understood [18]. The second phase (u 2 , k 2 ) was assumed to be determined by cadmium binding with calcium channels on the cell surface, because, on the one hand, cadmium is an inhibitor of calcium transport, on the other -this mechanism does not make significant contribution to the toxic effect of cadmium [13]. Finally, the last phase of cadmium accumulation (u 3 , V) is presumably determined by ZIP family transporters that work by the mechanism of electrodiffusion and perform slow unsaturated ion current [2] (Fig.…”

Development of an embryotoxicity test for Enchytraeus crypticus – The effect of Cd

“…zebrafish D. rerio (Hen Chow and Cheng, 2003), aquatic insect (Braeckman et al, 1999;Craig et al, 1999), and soil invertebrates species like H. aspersa (Druart et al, 2010) and Eisenia andrei (Li et al, 2010) or in mammalian cells (Blazka and Shaikh, 1991;Hinkle et al, 1987), and that Cd has a high affinity binding site in the L-type Ca channels (Marchetti, 2013;Misra et al, 2002). Additionally, in mammalian cells, it was shown that Cd induces gene transcription with consequent protein translation (Misra et al, 2002).…”