13 Neurotransmitter Clearance
After neurotransmitters have been released into the synaptic cleft, they act upon postsynaptic receptors, as covered in the previous chapters. That action must be terminated in order for proper neuronal communication to continue. This is accomplished mainly through two processes: neurotransmitter transport and/or degradation. Transport physically removes the neurotransmitter molecule from the synaptic cleft. Degradation breaks down the neurotransmitter molecule by enzyme activity.
Neurotransmitters can be degraded by enzymes in the synapse
Acetylcholine
Acetylcholine action is terminated by acetylcholinesterase, an enzyme present in the synaptic cleft. Acetylcholinesterase degrades acetylcholine into choline and acetate molecules. Choline is then transported back into the presynaptic terminal and used in the synthesis of new acetylcholine.
Neurotransmitters can be transported into glial cells and degraded by enzymes
Glutamate
Glutamate action is terminated by two mechanisms. Reuptake of glutamate molecules into the presynaptic terminal can occur, or glutamate can be transported into nearby glial cells. The excitatory amino acid transporters are sodium co-transporters and use the sodium electrochemical gradient to drive neurotransmitter transport. Within glial cells, glutamate is converted into glutamine by glutamine synthetase. Glutamine is then transported out of the glial cell and back into the presynaptic terminal for use in future glutamate synthesis. If glutamate is transported back into the presynaptic terminal, it can be repackaged in synaptic vesicles.
GABA and Glycine
Like glutamate, GABA and glycine action are terminated by either reuptake into the presynaptic terminal and packaging in synaptic vesicles or through transport into glial cells where breakdown can occur. The GABA and glycine transporter also use the sodium electrochemical gradient to drive the movement of the transmitter across the membrane.
Neurotransmitters can be transported back into the terminal and either degraded or repackaged
Dopamine
Dopamine action is terminated by reuptake into the presynaptic terminal via the dopamine transporter (DAT). Once inside the cell, dopamine is either degraded via the actions of either monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT), or it is repackaged into vesicles.
Norepinephrine
Norepinephrine follows the same pathway as dopamine. Reuptake into the presynaptic terminal occurs via the norepinephrine transporter (NET), and then the transmitter is either degraded within the cell by MAO or COMT or repackaged into synaptic vesicles.
Serotonin
Like the other monoamines, serotonin is transported back into the presynaptic terminal via the serotonin transporter (SERT). The difference between serotonin and the catecholamines dopamine and norepinephrine is that monoamine oxidase is the only enzyme used for degradation.
Conclusion
Effective neurotransmitter termination ensures precise and regulated neural communication. By recycling or breaking down neurotransmitters, the synapse is prepared for subsequent signaling, maintaining the dynamic balance critical for nervous system function.
Key Takeaways
- Neurotransmitter action in the synapse must be terminated
- This occurs by either
- reuptake into the presynaptic terminal where enzymatic degradation or repackaging into vesicles occurs
- transport into glial cells where enzymatic degradation occurs
- enzymatic degradation in the synapse
Important Terminology
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An enzyme present in the synaptic cleft that degrades acetylcholine into choline and acetate. Choline is then transported back into the presynaptic terminal.
An enzyme that degrades catecholamine neurotransmitters (dopamine and norepinephrine) in the presynaptic terminal.
Dopamine transporter, a protein that moves dopamine from the synaptic cleft back into the presynaptic terminal.
The breakdown of neurotransmitter molecules by enzyme activity. Degradation terminates neurotransmitter action.
A sodium co-transporter that moves glutamate from the synaptic cleft into either the presynaptic terminal or glial cells. Uses the sodium electrochemical gradient to drive glutamate transport.
A non-neuronal cell in the nervous system. Glial cells can take up neurotransmitters from the synaptic cleft and break them down enzymatically.
An enzyme in glial cells that converts glutamate into glutamine. Glutamine is then transported back to neurons for glutamate synthesis.
An enzyme that degrades monoamine neurotransmitters (dopamine, norepinephrine, serotonin) in the presynaptic terminal.
Norepinephrine transporter, a protein that moves norepinephrine from the synaptic cleft back into the presynaptic terminal.
The transport of neurotransmitters from the synaptic cleft back into the presynaptic terminal or into glial cells. Reuptake terminates neurotransmitter action.
Serotonin transporter, a protein that moves serotonin from the synaptic cleft back into the presynaptic terminal.
A transporter protein that uses the sodium electrochemical gradient to move another molecule across the membrane. Excitatory amino acid transporters and GABA/glycine transporters are sodium co-transporters.
