Calcium channels as target sites of heavy metals

Zinc (Zn), aluminium (Al), mercury (Hg), methylmercury (MeHg) and lead (Pb) extracellulary applied reduce voltage-activated calcium channel currents (VACCCs); Ph and Al also reduce N-methyl-D-aspartate (NMDA)-activated channel currents (NACCs). Pb is most effective in reducing VACCCs, with an IC50 of 0.46 mu M, followed by Hg (IC50 = 1.1 mu M) and MeHg (IC50 = 2.6 mu M). Zn and Al were less potent (IC50 = 69 and 84 mu M, respectively). Al acts on channels in the open state; its effect is pH dependent. The effects of Ph were specific for VACCCs and NACCs. Hg, Al and Zn had only minor effects on voltage-activated potassium and sodium channels, while MeHg reduced potassium channel currents (IC50 = 2.2 mu M) and, at higher concentrations, sodium channel currents (IC50 = 12.3 mu M). Al also reduced other receptor-activated channel currents. These results demonstrate that a variety of metal species produce different actions at the level of the cell membrane.