Synaptic vesicle

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Neuron A (transmitting) to neuron B (receiving)
1. Mitochondria
2. synaptic vesicle with neurotransmitters
3. Autoreceptor
4. Synapse with neurotransmitter released (serotonin)
5. Postsynaptic receptors activated by neurotransmitter (induction of a postsynaptic potential)
6. Calcium channel
7. Exocytosis of a vesicle
8. Recaptured neurotransmitter

In a neuron, synaptic vesicles, also called neurotransmitter vesicles, store the various neurotransmitters that are released during calcium-regulated exocytosis at the presynaptic terminal into the synaptic cleft of a synapse. The vesicles are essential for the propagation of nerve impulses between neurons and are constantly recreated by the cell.

Formation

Synaptic vesicles are made of a lipid bilayer in which transport proteins specific to each type of neurotransmitter are inserted. Neurotransmitters are moved from the cell's cytoplasm into the vesicles by vesicular transporters that rely on active transport mechanisms involving an exchange of protons (H+ ions). The necessary proton gradient is created by hydrogen ATPase, which breaks down ATP for energy. Vesicular glutamate transporters, for example, sequester glutamate into vesicles by this process.

The stoichiometry for the movement of different neurotransmitters into a vesicle is given in the following table.

Neurotransmitter type(s) Inward movement Outward movement
norepinephrine, dopamine, histamine, serotonin and acetylcholine neurotransmitter+ 2 H+
GABA and glycine neurotransmitter 1 H+
glutamate neurotransmitter- + Cl- 1 H+

Neurotransmitter release

Neurotransmitters are released when vesicles fuse with the cell's plasma membrane at "active zones" of a synapse. Vesicles are scattered throughout the synapse; some are docked at the active zones, but the majority are located away from them. When the action potential arrives at the synapse, the resulting increase in positive charge (depolarization) opens ion channels called voltage-gated calcium channels, allowing Ca++ to flow into the cell. The influx of Ca++ triggers a series of protein interactions, including SNAREs and Synaptotagmins, and causes the vesicle membrane to be fused with the presynaptic membrane at the active zone. The vesicles' membranes fuse with the presynaptic membrane, and the contents of the vesicles are released into the synaptic space.

Membrane material from the vesicles is recycled by the cell through endocytosis: either bulk endocytosis occurs, or clathrin-coated pits form, and the newly formed vesicles merge with endosomes. New vesicles bud off from endosomes after the material is processed [1]

The material in vesicles may also be released through the "kiss and run pathway", in which the vesicles only fuse slightly with the membrane, not integrating themselves fully into it. Instead they form a fusion pore, a small opening which is possibly made of two hemichannels, through which neurotransmitters may flow [1]. That way, the fusion pore can close and the cell need not go through the processes of exocytosis and endocytosis, making the kiss and run process the fastest means of vesicle recycling. However, less neurotransmitter is released this way, so it is mainly used when the synapse needs to release small amounts of material [1].

Enzymatic mechanism

Vesicles are normally tethered by proteins called synapsins to actin filaments or other cytoskeletal elements within the cell. The influx of Ca++ causes the activation of the Ca++/calmodulin-dependent protein kinase, which phosphorylates synapsin, causing it to release the vesicles from where they are tethered.

Newly released vesicles must be targeted to active sites, a job possibly carried out by proteins called Rab proteins, specifically Rab3A and Rab3C. Next the vesicles must be docked at the site from which their contents are to be released. One theory about how they accomplish this is that a protein on the vesicle, called a vesicle SNARE, or v-SNARE, binds with a similar protein, a target or t-SNARE, which is on the membrane where the vesicle is to dock. In order for the vesicle to be recycled after neurotransmitter release, the association between t- and v-SNARES must be undone. This process is accomplished by the cytoplasmic proteins N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (SNAP).

Effects of neurotoxins

Some neurotoxins, such as batrachotoxin, are known to destroy synaptic vesicles. The tetanus toxin damages vesicle-associated membrane proteins (VAMP), a type of v-SNARE, while botulinum toxins damage t-SNARES and v-SNARES and thus inhibit synaptic transmission.[1] A spider toxin called α-Latrotoxin binds to neurexins, damaging vesicles and causing massive release of neurotransmitters.

References

  1. 1.0 1.1 1.2 1.3 Kandel, E.R. (2000). Principles of Neural Science, 4th ed. New York: McGraw-Hill. pp. 269–273. ISBN 0-8385-7701-6. Unknown parameter |coauthors= ignored (help)

he:שלפוחית סינפטית


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