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

Figure 2

Effects of Metals on the cAMP Signaling Pathway at the Presynaptic Terminal (green: activation/increase, red: inhibition/decrease). GPCR’s are coupled to G_s or G_i/o, where G_s stimulates adenylate cyclase and G_i/o inhibits PKA. PKA phosphorylates Ca²⁺-channels, thereby enhancing the influx of Ca²⁺ and this increases the release of neurotransmitters. PKA phosphorylates SNAP-25 and this leads to a larger pool of readily releasable vesicles. The cAMP-system appears to enhance the release of neurotransmitter in response to a stimulus. Metals act at different points in this pathway either enhancing certain processes or inhibiting some. A green color indicates an activation or an increase, and a red color indicates an inhibition or a decrease.