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 Ca_v2.3 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 [259]).