Metal Toxicity at the Synapse: Presynaptic, Postsynaptic, and Long-Term Effects

Figure 3

Effects of metals on the PLC signaling pathway at presynaptic terminal (green: activation/increase, red: inhibition/decrease). The PLC system consists of GPCRs coupled to Gq, which activate PLC, which activates DAG and IP₃. IP₃ increases intracellular calcium ([Ca²⁺]_i) and activates DOC2 and synaptotagmin which leads to increased evoked release and readily releasable pool size. DAG activates PKC, which activates voltage-gated calcium channels. PKC phosphorylates Munc 18, which negatively regulates vesicle fusion and syntaxin. PKC activation leads to the increased spontaneous and evoked neurotransmitter release. The effects of metals on this pathway are shown in this figure where a green color indicates an activation/upregulation and a red color indicates an inhibition/downregulation.