An action potential cannot jump the narrow gap between two neurones. At a synapse the electrical signal is turned into a chemical one and back again: calcium ions trigger the release of acetylcholine, which crosses the cleft, binds to receptors and depolarises the next neurone, then is broken down and recycled.
A cholinergic synapse uses acetylcholine (ACh) as its neurotransmitter. The presynaptic knob contains many mitochondria and vesicles of ACh; it is separated from the postsynaptic membrane by a synaptic cleft about 20 nm wide. When an action potential arrives, voltage-gated Ca2+ channels open and Ca2+ diffuses into the knob. This makes vesicles move to and fuse with the presynaptic membrane, releasing ACh by exocytosis. ACh diffuses across the cleft and binds to receptor proteins on the postsynaptic membrane, opening Na+ channels; Na+ diffuses in and depolarises the membrane, and if threshold is reached an action potential is set up. Acetylcholinesterase in the cleft hydrolyses ACh to choline and ethanoic acid, which are taken back into the knob and recombined using ATP. Transmission is one-way because only the presynaptic side has vesicles and only the postsynaptic side has receptors.
Fig. 1: a cholinergic synapse, with vesicles of acetylcholine in the presynaptic knob and receptors on the postsynaptic membrane
Section 01
From impulse to chemical and back.
Press Send an action potential and read the stage readout as it changes: action potential arrives, Ca2+ channels open, vesicles fuse, ACh binds, postsynaptic depolarisation, ACh broken down. Watch the green Ca2+ ions, the yellow ACh and the orange Na+.
Structure
Role
presynaptic knob
swollen end of the axon; contains mitochondria (ATP for making ACh and for exocytosis), smooth ER and vesicles of ACh
voltage-gated Ca2+ channels
in the presynaptic membrane; open when it depolarises
synaptic cleft
gap of about 20 nm that ACh must diffuse across
ACh receptors
proteins in the postsynaptic membrane with a binding site complementary to ACh; they are ligand-gated Na+ channels
acetylcholinesterase
enzyme in the cleft (on the postsynaptic membrane) that hydrolyses ACh
1. Arrival: an action potential reaches the presynaptic knob and depolarises its membrane.
2. Calcium in: voltage-gated Ca2+ channels open; Ca2+ ions diffuse into the knob, down their concentration gradient.
3. Exocytosis: Ca2+ causes vesicles to move to and fuse with the presynaptic membrane, releasing ACh into the cleft.
4. Binding: ACh diffuses across the cleft and binds to receptors on the postsynaptic membrane, which open.
5. Depolarisation: Na+ diffuses into the postsynaptic neurone. If enough ACh binds to reach threshold, an action potential is set up.
6. Removal: acetylcholinesterase hydrolyses ACh into choline and ethanoic acid, so the receptors close and the signal stops. Choline diffuses back into the knob and is combined with ethanoyl (acetyl) coenzyme A to make new ACh, using ATP.
Examiner trap
Calcium ions do not cross the cleft and do not bind to the postsynaptic receptors. Ca2+ acts inside the presynaptic knob, triggering vesicle fusion. It is ACh that diffuses across the cleft.
Stage 1 · Learn
Check what the sim just showed you
Four quick checks. Each correct answer earns XP and records this skill on your profile.
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In the synapse simulator, what is the second stage after the action potential arrives?
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In the simulator, what happens to the yellow ACh in the final stage?
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What do the ACh receptors on the postsynaptic membrane do when ACh binds?
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Why does the simulator show the signal crossing only from the knob to the postsynaptic membrane?
Section 02
Why synapses matter.
Run the synapse simulator again and notice where the vesicles are and where the receptors are. That arrangement explains why the signal can only cross one way.
One-way transmission: vesicles of ACh are only in the presynaptic knob and receptors are only on the postsynaptic membrane, so impulses cross in one direction.
Threshold and summation: one vesicle's worth of ACh may not depolarise the postsynaptic membrane enough; several impulses in quick succession, or from several presynaptic neurones, can add together to reach threshold. This filters out weak, low-frequency signals.
Integration: one neurone can receive synapses from many others, so information from different sources can be combined in the CNS.
Stopping the signal: rapid breakdown of ACh by acetylcholinesterase stops the postsynaptic membrane from being depolarised continuously, so each impulse gives a separate response.
Synaptic delay: diffusion of ACh across the cleft is slower than conduction along an axon, so each synapse adds a short delay (about 0.5 ms).
Examiner trap
Choline is recycled, but it is reabsorbed into the presynaptic knob, not the postsynaptic neurone. The postsynaptic neurone does not store or release ACh at this synapse.
Stage 2 · Exam
Exam-style questions
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A toxin prevents calcium ions entering the presynaptic knob. What is the most likely effect?
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Some insecticides inhibit acetylcholinesterase. Which effect on a cholinergic synapse would you expect?
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Why does a presynaptic knob contain many mitochondria?
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A single impulse in a presynaptic neurone fails to produce an action potential in the postsynaptic neurone. Which best explains this?
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The cholinergic synapse, mastered.
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