- How a chemical synapse is structured and why it makes transmission one-way.
- The step-by-step role of calcium ions, synaptic vesicles and neurotransmitters.
- How excitatory and inhibitory synapses affect whether a postsynaptic neurone fires.
- How drugs and poisons can alter synaptic transmission.
A neurone is a specialised cell that transmits information in the nervous system. Along a neurone’s axon, information travels as an action potential: a brief, rapid change in membrane potential caused by movement of ions across the cell surface membrane.
The issue is that neurones usually do not physically touch each other. The action potential cannot simply “jump” electrically from one neurone to the next. Instead, most neurones communicate at a tiny junction called a synapse.
Synapse
A synapse is a junction between two neurones, or between a neurone and an effector such as a muscle cell, where a signal is transmitted from one cell to another.
At A-Level, the main type you need is the chemical synapse, where an electrical signal is converted into a chemical signal and then back into an electrical signal.
The neurone before the synapse is the presynaptic neurone. Its swollen axon ending is often called the synaptic knob. The cell after the synapse is the postsynaptic neurone or postsynaptic cell.
Between them is a tiny gap called the synaptic cleft, usually only tens of nanometres wide. The presynaptic knob contains synaptic vesicles, which are small membrane-bound sacs containing a chemical messenger called a neurotransmitter.
The labelled diagram below shows the key structures and the sequence of events in synaptic transmission.

Synapses are one-way
Chemical synapses normally transmit in one direction because synaptic vesicles are found in the presynaptic knob, while the matching receptor proteins are on the postsynaptic membrane.
When an action potential reaches the presynaptic knob, it triggers a carefully controlled sequence:
- The action potential arrives and depolarises the presynaptic membrane. Depolarisation means the inside of the membrane becomes less negative than usual.
- Voltage-gated calcium ion channels open. These are channel proteins that open in response to a change in membrane potential.
- Calcium ions, Ca²⁺, diffuse into the synaptic knob down their electrochemical gradient.
- The calcium ions cause synaptic vesicles to move towards and fuse with the presynaptic membrane.
- The neurotransmitter is released into the synaptic cleft by exocytosis, which is the release of substances from a cell when vesicles fuse with the cell surface membrane.
- The neurotransmitter diffuses across the synaptic cleft.
- The neurotransmitter binds to specific receptor proteins on the postsynaptic membrane. The receptors have a complementary shape to the neurotransmitter.
- In an excitatory synapse, this opens ligand-gated sodium ion channels. A ligand is a molecule that binds to a receptor.
- Sodium ions, Na⁺, diffuse into the postsynaptic neurone, causing depolarisation.
- If the depolarisation reaches threshold at the start of the postsynaptic axon, a new action potential is generated.
Predicting the effect of blocking calcium channels
A toxin blocks voltage-gated calcium ion channels in the presynaptic membrane. Predict the effect on synaptic transmission.
- Calcium ions normally enter the synaptic knob after an action potential arrives, so blocking the channels prevents Ca²⁺ influx.
- Without Ca²⁺ influx, synaptic vesicles are much less likely to fuse with the presynaptic membrane.
- Less neurotransmitter is released into the synaptic cleft, so fewer postsynaptic receptors are activated.
- The postsynaptic membrane is less likely to depolarise to threshold, so transmission across the synapse is reduced or stopped.
A neurotransmitter is a chemical released by a presynaptic neurone that affects a postsynaptic cell. One important example is acetylcholine, often shortened to ACh.
A synapse that uses acetylcholine is called a cholinergic synapse. Acetylcholine is especially important at the neuromuscular junction, which is the synapse between a motor neurone and a muscle fibre.
At a cholinergic synapse:
- Acetylcholine is released from vesicles in the presynaptic knob.
- It diffuses across the synaptic cleft.
- It binds to acetylcholine receptors on the postsynaptic membrane.
- Sodium ion channels open, causing depolarisation.
- Acetylcholine is then broken down by the enzyme acetylcholinesterase.
This breakdown is essential. If acetylcholine stayed in the synaptic cleft, it would keep binding to receptors and the postsynaptic cell could be stimulated continuously.
Forgetting neurotransmitter removal
Do not stop your description at “neurotransmitter binds to receptors”. For a full answer, include how the neurotransmitter is removed, such as enzymic breakdown or reuptake.
Not every synapse makes the next neurone fire. Synapses can be excitatory or inhibitory.
An excitatory postsynaptic potential, or EPSP, is a small depolarisation of the postsynaptic membrane. It makes the postsynaptic neurone more likely to reach threshold and fire an action potential.
An inhibitory postsynaptic potential, or IPSP, makes the postsynaptic neurone less likely to fire. This may happen if chloride ions, Cl⁻, enter the cell or potassium ions, K⁺, leave the cell, making the inside more negative. This is called hyperpolarisation.
Threshold
The threshold is the membrane potential that must be reached to trigger an action potential. In many neurones it is around -55 mV, although the exact value varies.
A single EPSP is often too small to reach threshold. Instead, the postsynaptic neurone adds together multiple inputs. This is called summation.
The diagram below shows how EPSPs and IPSPs can combine at the postsynaptic neurone.

Temporal summation happens when several action potentials arrive in quick succession from the same presynaptic neurone. The EPSPs overlap in time, so their effects add together.
Spatial summation happens when action potentials arrive from several different presynaptic neurones at about the same time. Their combined effects are added at the postsynaptic neurone, especially near the axon hillock, the region where a new action potential is most likely to start.
Deciding whether threshold is reached
A postsynaptic neurone has a resting potential of -70 mV and a threshold of -55 mV. Three EPSPs change the membrane potential by +6 mV, +5 mV and +4 mV. One IPSP changes it by -3 mV. Decide whether an action potential is generated.
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Add the excitatory effects:
6 mV+5 mV+4 mV=15 mV6\ \text{mV} + 5\ \text{mV} + 4\ \text{mV} = 15\ \text{mV}6 mV+5 mV+4 mV=15 mV
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Include the inhibitory effect:
15 mV−3 mV=12 mV15\ \text{mV} - 3\ \text{mV} = 12\ \text{mV}15 mV−3 mV=12 mV
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Add the net change to the resting potential:
new membrane potential=−70 mV+12 mV=−58 mV\text{new membrane potential} = -70\ \text{mV} + 12\ \text{mV} = -58\ \text{mV}new membrane potential=−70 mV+12 mV=−58 mV
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Compare with threshold. -58 mV is still more negative than -55 mV, so threshold is not reached and no action potential is generated.
Use precise wording
For EPSPs, say “more likely to fire” unless threshold is definitely reached. A small depolarisation is not automatically a new action potential.
Synapses do more than pass on messages. They allow the nervous system to process information.
Synapses can:
- Make transmission one-way.
- Allow one neurone to communicate with many others.
- Allow many neurones to influence one postsynaptic neurone.
- Filter out weak stimuli that do not reach threshold.
- Allow inhibition, which is essential for controlling responses.
- Be modified during learning and memory.
This ability of synapses to change in strength is part of synaptic plasticity. Plasticity means the nervous system can change its connections or responses as a result of activity or experience.
Because synapses depend on specific proteins and chemicals, they are common targets for drugs and poisons.
An agonist is a substance that binds to a receptor and activates it, mimicking the normal neurotransmitter. An antagonist binds to a receptor but does not activate it, so it blocks the neurotransmitter from binding.
A reuptake inhibitor prevents neurotransmitter being taken back into the presynaptic neurone. For example, selective serotonin reuptake inhibitors, or SSRIs, reduce serotonin reuptake. This means serotonin remains in the synaptic cleft for longer and can continue binding to receptors.
An enzyme inhibitor can also alter synaptic transmission. If acetylcholinesterase is inhibited, acetylcholine is broken down more slowly, so stimulation of the postsynaptic membrane lasts longer.
Predicting the effect of inhibiting acetylcholinesterase
A drug inhibits acetylcholinesterase at a cholinergic synapse. Predict its effect.
- Acetylcholinesterase normally breaks down acetylcholine in the synaptic cleft, stopping it from repeatedly binding to receptors.
- If the enzyme is inhibited, acetylcholine remains in the synaptic cleft for longer.
- Acetylcholine can keep binding to receptors, so ligand-gated sodium ion channels stay open for longer.
- The postsynaptic membrane remains depolarised for longer, which can cause repeated firing or prolonged muscle contraction.
Saying neurotransmitters are always excitatory
The effect of a neurotransmitter depends on the receptor and ion channels involved. Some synapses are excitatory, while others are inhibitory.
Chemical synapses are slower than electrical conduction along an axon. This is because vesicles must fuse, neurotransmitter must diffuse across the cleft, and receptors must be activated.
This delay is usually very short, often around 0.5 ms, but it matters. Pathways with fewer synapses, such as simple reflex arcs, can produce very rapid responses.
In the exam
- For transmission across a synapse, give the sequence in order: action potential arrives, Ca²⁺ enters, vesicles fuse, neurotransmitter diffuses, receptors bind, ion channels open, postsynaptic membrane depolarises.
- Always link a drug or toxin to its exact target, such as calcium channels, receptors, reuptake transporters or acetylcholinesterase.
- When discussing EPSPs and IPSPs, compare the final membrane potential with threshold before saying whether an action potential is generated.
Check yourself
- Why does calcium ion entry into the synaptic knob lead to neurotransmitter release?
- How does acetylcholinesterase stop continuous stimulation at a cholinergic synapse?
- What is the difference between temporal summation and spatial summation?