What causes the release of neurotransmitter into the synaptic cleft?
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Once loaded with transmitter molecules, vesicles associate with the presynaptic membrane and fuse with it in response to Ca2+ influx, as described in Chapter 5. The mechanisms of vesicle release are similar for all transmitters, although there are differences in the speed of this process. In general, small-molecule transmitters are secreted more rapidly than peptides. For example, while secretion of ACh from motor neurons requires only a fraction of a millisecond, many neuroendocrine cells, such as those in the hypothalamus, require high-frequency bursts of action potentials for many seconds to release peptide hormones from their nerve terminals. These differences in the rate of transmitter release make neurotransmission rapid at synapses employing small-molecule transmitters and relatively slow at synapses that use peptides. As already mentioned, these differences in the rate of release probably arise from spatial differences in vesicle localization and presynaptic Ca2+ signaling (see Figure 6.5). Thus, the small clear-core vesicles used to store small-molecule transmitters are often docked at active zones (specialized regions of the presynaptic membrane; see Chapter 5), whereas the large dense-core vesicles used to store peptides are not (compare Figure 6.7A and B). Since biogenic amines are sometimes packaged into small vesicles that dock at active zones and are sometimes packaged and released much like peptides, the speed of their release can vary greatly. Show When the neurotransmitter has been secreted into the synaptic cleft, it binds to specific receptors on the postsynaptic cell, thereby generating a postsynaptic electrical signal, as described in much more detail in Chapter 7. The transmitter must then be removed rapidly to enable the postsynaptic cell to engage in another cycle of neurotransmitter release, binding, and signal generation. The mechanisms by which neurotransmitters are removed vary but always involve diffusion in combination with reuptake into nerve terminals or surrounding glial cells, degradation by transmitter-specific enzymes, or in some cases a combination of these mechanisms. For most of the small-molecule neurotransmitters, specific transporter proteins remove the transmitters (or their metabolites) from the synaptic cleft, ultimately delivering them back to the presynaptic terminal for reuse (see Figure 6.6A). The particulars of synthesis, packaging, release and removal differ for each neurotransmitter. These variations are elaborated for the major neurotransmitters in the following sections, and are summarized in Table 6.1.  Table 6.1Functional Features of the Major Neurotransmitters.
Review . 2001 May;24(5):581-601. doi: 10.1002/mus.1044. Affiliations
Review Molecular mechanisms of neurotransmitter releaseE A Fon et al. Muscle Nerve. 2001 May. AbstractThe release of neurotransmitter from neurons represents one of the pivotal events in synaptic transmission. Neurotransmitters are released from synaptic vesicles in presynaptic neurons in response to neural activity, diffuse across the synaptic cleft, and bind specific receptors in order to bring about changes in postsynaptic neurons. Some of the molecular processes that govern neurotransmitter release are now becoming better understood. The steps involved can be broken down into two partially overlapping presynaptic cycles, the neurotransmitter cycle and the synaptic vesicle cycle. The neurotransmitter cycle involves transmitter biosynthesis, storage, reuptake, and degradation. The synaptic vesicle cycle involves targeting to the nerve terminal, docking, fusion, endocytosis, and recycling. Biochemical and structural studies have yielded important insight into our understanding of each of these two cycles. Further, both pharmacological and genetic interference with either of these cycles results in profound alterations in synaptic transmission and behavior, demonstrating the crucial role of neurotransmitter release. Copyright 2001 John Wiley & Sons, Inc. Similar articles
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