What Factors Affect the Release of Neurotransmitters?

Neurotransmitter (English neurotransmitter) is a specific chemical substance that acts as a "messenger" in synaptic transmission, referred to as a transmitter. With the development of neurobiology, a large number of neuroactive substances have been found in the nervous system. ^[1]

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Neurotransmitters must meet the following criteria:

1. Synthesis in neurons.

2. Stored in presynaptic neurons and

Neurotransmitters in the brain are divided into four categories, namely biological protoamines, amino acids, peptides, and others. Biogenic amine neurotransmitters are among the first to be discovered, including:

Synaptic transmission is accomplished through the release of chemical transmitters from the presynaptic membrane (non-synaptic

Cholinergic

It has long been believed that there is only one transmitter in a neuron, and all nerve endings release the same transmitter. This principle is called the Dale's principle. by

Synthesis of neurotransmitters

Acetylcholine is synthesized from choline and acetyl-CoA under the catalysis of choline acetyltransferase (choline acetylase). Since the enzyme is present in the cytoplasm, acetylcholine is synthesized in the cytoplasm, which is taken up and stored by vesicles after synthesis. The synthesis of norepinephrine is based on tyrosine. Dopa is first synthesized under the catalysis of tyrosine hydroxylase, and then dopamine (catechol B) is synthesized under the action of dopa decarboxylase (amino acid deendase). Amine), these two steps are performed in the cytoplasm; then dopamine is taken up into the vesicles, which is further catalyzed by dopamine beta hydroxylase to synthesize norepinephrine and stored in the vesicles. The synthesis of dopamine is exactly the same as the first two steps of norepinephrine, except that norepinephrine is no longer synthesized after dopamine enters the vesicles, because the dopamine-containing vesicles do not contain dopamine beta hydroxylase. The synthesis of serotonin uses tryptophan as a raw material. First, 5-hydroxytryptophan is synthesized under the action of tryptophan hydroxylase, and then 5-hydroxytryptamine is under the action of serotonin decarboxylase (amino acid decarboxylase). The two steps of serotonin synthesis by amino acid are performed in the cytoplasm; serotonin is then taken into the vesicles and stored in the vesicles. -aminobutyric acid is synthesized by glutamic acid under the action of glutamic acid decarboxylation. The synthesis of peptide transmitters is exactly the same as the synthesis of other peptide hormones. It is regulated by genes and synthesized on the ribosome through translation.

Neurotransmitter release

When the nerve impulse reaches the periphery, the periphery generates action potentials and ion transfer Ca2 + into the membrane from the outside of the membrane, causing a certain number of vesicles to fuse tightly with the presynaptic membrane. At the rupture, the transmitter and other contents of the vesicles are released into the synaptic cleft. The process by which presynaptic membranes release transmitters is called exocytosis or fission. In this process, the transfer of Ca2 + is important. If the extracellular Ca2 + concentration is reduced, the transmitter release is inhibited; while increasing the extracellular Ca2 + concentration increases the transmitter release. This fact indicates that the amount of Ca2 + entering the membrane from the outside of the membrane is directly related to the amount of transmitter release; Ca2 + is a necessary factor for the close fusion of the vesicle membrane and the presynaptic membrane. It is generally believed that Ca2 + may have two effects:

Decreasing the viscosity of axillary slurry is beneficial to the movement of small vesicles;

Eliminate the negative potential in the presynaptic membrane and facilitate the fusion of the vesicles with the presynaptic membrane. When the vesicles are ruptured to release the transmitter and other contents into the synaptic cleft, its shell can still remain in the presynaptic membrane (it can also fuse with the presynaptic membrane to become a part of the presynaptic membrane), and it will remain It can be restored to its original state and continue to synthesize and store the transmitter.

From the exocytosis of synaptic vesicles to the recovery of vesicle membranes can be divided into the following 6 phases:

Synaptic vesicles move into the presynaptic membrane active zone;

The vesicles abut the structure of the synaptic fence;

The vesicles are in contact with the presynaptic membrane and the two membranes are fused;

Fusion membrane dehiscence releases neurotransmitters to the synaptic cleft;

The vesicle membrane is incorporated into the presynaptic membrane;

The vesicle membrane is recovered and reused. During the cycle of vesicle membranes, some membranes do not form functional vesicles that do not enter the cycle but are degraded by lysosomes and returned to the cell body for reprocessing through reverse axonal transport. At the same time, new vesicles are delivered to the nerve endings by forward axoplasmic transport.

Immediately after the neurotransmitter is released from the presynaptic membrane, it binds to the corresponding postsynaptic membrane receptor, generating a synaptic depolarization potential or a hyperpolarization potential. Causes post-synaptic nerve excitability to increase or decrease. Since then, the electrical signals of nerve impulses have completed a leap across synapses.

Transmitter release process

Neurotransmitter inactivation

After entering the synaptic space, acetylcholine acts on the post-synaptic membrane to exert physiological effects, and is hydrolyzed by cholinesterase to choline and acetic acid, so that acetylcholine is destroyed and promotes the action, a process called inactivation. After norepinephrine enters the synaptic cleft and exerts physiological effects, part of it is taken away by the blood circulation, and then destroyed and inactivated in the liver; the other part is caused by catecholamine methyltransferase and monoamine oxidase in effector cells It is destroyed and inactivated by the action; but most of it is the re-uptake of norepinephrine by the presynaptic membrane, which is recovered into the axon at the presynaptic membrane and reused. The inactivation of dopamine is similar to the inactivation of norepinephrine. It is also destroyed and inactivated by the action of catecholamine methyl position shift enzyme and monoamine oxidase. The presynaptic membrane can also take up dopamine for reuse. The inactivation of serotonin is also similar to the inactivation of norepinephrine. Monoamine oxidase can degrade and destroy serotonin, and the presynaptic membrane can retake serotonin for reuse. Amino acid transmitters can be re-uptaked by neurons and glial cells and become inactivated. Peptide transmitters are inactivated by enzymatic degradation, such as by aminopeptidase, carboxypeptidase, and some endopeptidases.