Figure 6-3. Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent carrier (A). This transport can be inhibited by hemicholinium drugs. ACh is transported into the storage vesicle by a second carrier (B) that can be inhibited by vesamicol. Peptides (P), ATP, and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of ACh and cotransmitters into the junctional cleft. This step is blocked by botulinum toxin. Acetylcholine's action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending regulate transmitter release. (SNAPs, synaptosome-associated proteins; VAMPs, vesicle-associated membrane proteins.)
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