Fig. (2) Functional interaction of divalent heavy metal ions (Zn2+) and various ion channels and transporters within the hippocampal CA3 region. Mossy fiber terminals carry both Zn2+ and glutamate containing vesicles. Upon presynaptic excitation, glutamate and zinc are released into the synaptic cleft. Zn2+ exerts numerous effects on AMPA and NMDA receptors, GABA receptors and transporters. Voltage-gated Ca2+ channels, particularly Cav2.3 VGCCs turned out to be of central relevance. Note that both Ca2+ and Zn2+ that enter the cell exert complex effects on intracellular signal transduction cascades (reprinted from ).