As we have covered, when an action potential propagates down the axon to the presynaptic terminal, the electrical signal will result in a release of chemical neurotransmitters that will communicate with the postsynaptic cell.
Animation 10.1. The action potential is a brief but significant change in electrical potential across the membrane. The membrane potential will move from a negative, resting membrane potential, shown here as -65 mV, and will rapidly become positive and then rapidly return to rest during an action potential. The action potential moves down the axon beginning at the axon hillock. When it reaches the synaptic terminal, it causes the release of chemical neurotransmitter. ‘Action Potential Propagation’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License. View static image of animation
Ion flow in Terminal
When the action potential reaches the terminal, there is an influx of sodium ions. This inward current causes a depolarization of the terminal, activating voltage-gated calcium channels. There is a strong electrochemical gradient that moves calcium into the terminal.
Animation 10.2. An action potential causes an influx of sodium in the terminal. The depolarization opens voltage-gated calcium channels, and calcium ions flow into the terminal down their electrochemical gradient. The blue, dotted channels represent voltage-gated sodium channels, and the purple, striped channels represent voltage-gated calcium channels. ‘Terminal Calcium Influx’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC-BY-NC-SA) 4.0 International License. View static image of animation.
The voltage-gated calcium channels are concentrated in the presynaptic terminal at active zones, the regions of the membrane where small molecule neurotransmitters are released. At active zones, some synaptic vesicles are docked and are ready for immediate release upon arrival of the action potential. Other neurotransmitter-filled vesicles remain in a reserve pool outside of the active zone.
Vesicles filled with neuropeptides do not dock at active zones. They are located outside of the active zone, further away from the membrane and the high density of voltage-gated calcium channels and are therefore slower to release than the small molecule transmitters.
Docking of synaptic vesicles packaged with small molecule neurotransmitters occurs through the interaction of three membrane-bound proteins called SNARE proteins. Synaptobrevin is called a v-SNARE because it is located on the Vesicular membrane. Syntaxin and SNAP-25 are called t-SNARES because they are located on the terminal membrane, which is the Target membrane. The interaction of these three proteins leads to vesicle docking at the active zone.
The influx of calcium through the voltage-gated calcium channels initiates the exocytosis process that leads to neurotransmitter release. Calcium enters the cell and interacts with another vesicle-bound protein called synaptotagmin. This protein is a calcium sensor, and when calcium is present at the active zone, synaptotagmin interacts with the SNARE proteins. This is the first step toward exocytosis of the synaptic vesicle.
After exocytosis of the transmitter molecules, they enter the synaptic cleft and bind to receptors on the postsynaptic membrane. Receptors fall into two main categories: ligand-gated channels and G-protein coupled receptors. The next two chapters cover these receptors.
Neurotransmitter release is dependent on the influx of calcium into the terminal
SNARE proteins are important for vesicle docking at active zones and exocytosis