PMID: 8463062Jan 1, 1993Paper

Acetylcholine transport, storage, and release

International Review of Neurobiology
S M ParsonsI G Marshall

Abstract

ACh is released from cholinergic nerve terminals under both resting and stimulated conditions. Stimulated release is mediated by exocytosis of synaptic vesicle contents. The structure and function of cholinergic vesicles are becoming known. The concentration of ACh in vesicles is about 100-fold greater than the concentration in the cytoplasm. The AChT exhibits the lowest binding specificity among known ACh-binding proteins. It is driven by efflux of protons pumped into the vesicle by the V-type ATPase. A potent pharmacology of the AChT based on the allosteric VR has been developed. It has promise for clinical applications that include in vivo evaluation of the density of cholinergic innervation in organs based on PET and SPECT. The microscopic kinetics model that has been developed and the very low transport specificity of the vesicular AChT-VR suggest that the transporter has a channel-like or multidrug resistance protein-like structure. The AChT-VR has been shown to be tightly associated with proteoglycan, which is an unexpected macromolecular relationship. Vesamicol and its analogs block evoked release of ACh from cholinergic nerve terminals after a lag period that depends on the rate of release. Recycling quanta of ACh that...Continue Reading

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