Acetylcholine synapse formation

Tyrosine phosphorylation has a role in the formation of the neuromuscular synapse. For instance, the acetylcholine receptor (AChR) is concentrated at the postsynaptic membrane of the neuromuscular junction at a density of 10,000 receptors/pm2, which is about three orders of magnitude higher than that of the extrasynaptic region... 

Stimulus-evoked, calcium-dependent release of acetylcholine (ACh) from the cholinergic synapse normally occurs through the formation of a fusion complex between ACh-containing vesicles and the intracellular leaflet of the nerve terminal membrane (Amon et al., 2001). This synaptic vesicle fusion complex consists of several proteins of the SNARE family, including a 25 kDa synaptosomal associated protein (SNAP-25), vesicle-associated membrane protein (VAMP, or synaptobrevin), and the synaptic membrane protein syntaxin. Other SNARE proteins have been identified as components of membrane transport systems in yeast and mammals but have not been implicated as targets for BoNTs. Meanwhile, type A and E neurotoxins cleave SNAP-25 while types B, D, F, and G act on VAMP and type C1 toxin cleaves both syntaxin and SNAP-25. Neurotoxin-mediated cleavage of any of these substrates disrupts the processes involved in the exocytotic release of ACh and leads to flaccid paralysis of the affected skeletal muscles. 

More than 30 different substances have been proven or proposed to act as neurotransmitters. Neurotransmitters are either excitatory or inhibitory. As noted, excitatory neurotransmitters (e.g., glutamate and acetylcholine) open sodium channels and promote the depolarization of the membrane in another cell (either another neuron or an effector cell, such as a muscle cell). If the second (post-synaptic) cell is a neuron, the wave of depolarization (referred to as an action potential) triggers the release of neurotransmitter molecules as it reaches the end of the axon. (Most neurotransmitter molecules are stored in numerous membrane-enclosed synaptic vesicles.) When the action potential reaches the nerve ending, the neurotransmitter molecules are released by exocytosis into the synapse. If the postsynaptic cell is a muscle cell, sufficient release of excitatory neurotransmitter molecules results in muscle contraction. Inhibitory neurotransmitters (e.g., glycine) open chloride channels and make the membrane potential in the postsynaptic cell even more negative, that is, they inhibit the formation of an action potential. 

Galzigna has recently demonstrated the possibility of complex formation between acetylcholine and noradrenochrome [199, 200]. This led to the proposal of the short circuit theory to explain the onset of mental illness [200, 201]. According to this theory, if a central catecholamine were leaking from a synapse, in the absence of the enzyme system which normally destroys it, it could be oxidised to the aminochrome, which then forms a stable... 

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