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.

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.

Illustrated pathway of acetylcholine degradation. Details in caption.
Figure 13.1. Acetylcholine is degraded into choline and acetate within the synaptic cleft via acetylcholinesterase. Choline is then transported back into the presynaptic terminal. ‘Acetylcholine Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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.

Illustrated pathway of glutamate degradation. Details in caption.
Figure 13.2. Glutamine needs to removed from the synapse. The excitatory amino acid transporter that uses sodium to drive glutamate movement across the membrane can move glutamate into glial cells or back into the presynaptic terminal. In the terminal, glutamate is repackaged into synaptic vesicles. In the glial cells, glutamate is broken down into glutamine by glutamine synthetase. ‘Glutamate Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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.

Illustrated pathway of GABA and glycine degradation. Details in caption.
Figure 13.3. GABA and glycine action is terminated by reuptake by sodium co-transporters into either glial cells or back into the presynaptic terminal. In both locations, the neurotransmitters can be broken down by enzymes, whereas in the presynaptic terminal, the transmitters can be repackaged in synaptic vesicles. ‘GABA and Glycine Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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.

Illustrated pathway of dopamine degradation. Details in caption.
Figure 13.4. Dopamine action is terminated by reuptake into the presynaptic terminal via DAT. Dopamine is then either degraded by MAO or COMT or repackaged into synaptic vesicles. ‘Dopamine Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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.

Illustrated pathway of norepinephrine degradation. Details in caption.
Figure 13.5. Norepinephrine action is terminated by reuptake into the presynaptic terminal via NET. Norepinephrine is then either degraded by MAO or COMT or repackaged into synaptic vesicles. ‘Norepinephrine Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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.

Illustrated pathway of serotonin degradation. Details in caption.
Figure 13.6. Serotonin action is terminated by reuptake into the presynaptic terminal via SERT. Serotonin is then either degraded by MAO or repackaged into synaptic vesicles. ‘Serotonin Degradation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License.

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

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