SPEC 3.6.2.2 - RESPONSES
Synaptic Transmission
Cholinergic synapses, the neuromuscular junction, summation and inhibition — how chemical signals cross the gap
Key Definitions
Synapse
A junction between two neurones (or a neurone and an effector) across which nerve impulses are transmitted chemically.
Neurotransmitter
A chemical released from synaptic vesicles into the synaptic cleft that binds to receptors on the postsynaptic membrane.
Acetylcholine (ACh)
The neurotransmitter at cholinergic synapses and neuromuscular junctions. Released by exocytosis from the presynaptic terminal.
Exam Technique
When the examiner asks you to describe transmission, name every molecule. "A neurotransmitter" loses marks — "acetylcholine" wins marks.
Structure of a Cholinergic Synapse
A synapse has three key structural components the examiner expects you to name precisely:
StructureDescriptionFunction
Presynaptic terminal (knob)Bulge at end of presynaptic neurone; contains mitochondria and synaptic vesiclesSynthesises and stores ACh; provides ATP for resynthesis
Synaptic cleftNarrow fluid-filled gap between pre- and postsynaptic membranesACh diffuses across; contains acetylcholinesterase
Postsynaptic membraneMembrane of the next cell (neurone or muscle)Bears complementary ACh receptors linked to Na⁺ channels
Synaptic vesiclesMembrane-bound spheres in presynaptic terminalContain ACh; fuse with presynaptic membrane on stimulation
Examiner Alert
Students frequently call synaptic vesicles "acetylcholine" or "neurotransmitter" in labelling questions. The vesicle is the structure; acetylcholine is the contents. These are different marks.
Transmission Across a Cholinergic Synapse
Learn this as a numbered sequence — the examiner expects mechanism, not just outcomes:
1
Action potential arrives at the presynaptic terminal
2
Voltage-gated Ca²⁺ channels open → Ca²⁺ ions diffuse into the terminal down their concentration gradient
3
Ca²⁺ ions cause synaptic vesicles to move to and fuse with the presynaptic membrane → ACh released by exocytosis
4
ACh diffuses across the synaptic cleft (down its concentration gradient)
5
ACh binds to complementary receptors on the postsynaptic membrane → Na⁺ channels open → Na⁺ influx → depolarisation → EPSP (excitatory postsynaptic potential)
6
Acetylcholinesterase (in the synaptic cleft) hydrolyses ACh → choline + ethanoate — signal terminated
7
Choline reabsorbed into presynaptic terminal → ACh resynthesised using ATP
Why Synapses are Unidirectional
The examiner regularly asks students to explain unidirectionality — not just state it.
Structural Reason 1
Synaptic vesicles (containing ACh) are only present in the presynaptic terminal — not the postsynaptic cell.
Structural Reason 2
ACh receptors are only on the postsynaptic membrane — not on the presynaptic membrane.
Exam Technique
State both reasons for full marks: "Synaptic vesicles are only present presynaptically, and receptors are only on the postsynaptic membrane, so ACh can only act in one direction."
Role of Acetylcholinesterase
Rapid hydrolysis of ACh by acetylcholinesterase ensures the signal is discrete and terminated — prevents continuous stimulation and allows the synapse to be reused.
Summation
Summation
The summation of excitatory and inhibitory postsynaptic potentials to determine whether the membrane potential reaches the threshold required to generate an action potential. EPSPs are graded potentials — their size varies with the stimulus, which is why they can add together.
A single EPSP is usually subthreshold — it alone cannot trigger an action potential. Summation allows weak or infrequent signals to be integrated.
Temporal Summation
Rapid successive impulses arrive from one presynaptic neurone — EPSPs accumulate before they decay → threshold reached.
Think: time-based — same neurone firing repeatedly
Spatial Summation
Simultaneous impulses arrive from multiple presynaptic neurones — EPSPs from different synapses sum → threshold reached.
Think: space-based — many neurones firing together
Examiner Alert
Many students confuse temporal and spatial summation. The key difference: temporal = one neurone, repeated; spatial = many neurones, simultaneous.
Inhibitory Synapses
Not all synapses excite — inhibitory synapses reduce the chance of generating an action potential in the postsynaptic cell.
1
Inhibitory neurotransmitter (e.g. GABA) released from presynaptic terminal
2
Binds to receptors on postsynaptic membrane → Cl⁻ channels open
3
Cl⁻ ions flow into the postsynaptic cell → membrane becomes more negative (hyperpolarisation)
4
Membrane potential moves further from threshold → harder to generate action potential → inhibition of postsynaptic cell
IPSP vs EPSP
An IPSP (inhibitory postsynaptic potential) is the opposite of an EPSP — it hyperpolarises rather than depolarises the postsynaptic membrane. The net effect on the postsynaptic cell is determined by the balance of EPSPs and IPSPs received simultaneously.
The Neuromuscular Junction (NMJ)
Neuromuscular Junction
The synapse between a motor neurone and a skeletal muscle fibre. It is always excitatory and uses acetylcholine as its neurotransmitter.
Events at the NMJ:
1
AP arrives at motor neurone terminal → voltage-gated Ca²⁺ channels open → Ca²⁺ enters
2
ACh released by exocytosis → diffuses across cleft → binds to receptors on sarcolemma (muscle fibre membrane)
3
Na⁺ channels on sarcolemma open → depolarisation → AP generated across sarcolemma and T-tubules
4
AP travels deep into muscle fibre via T-tubules → Ca²⁺ released from sarcoplasmic reticulum → muscle contraction triggered
Key Term
The muscle fibre membrane is called the sarcolemma. Use this precise term — not just "muscle membrane."
NMJ vs Cholinergic Synapse
The AQA spec requires you to be able to compare these two structures:
FeatureCholinergic Synapse (neuronal)Neuromuscular Junction
NeurotransmitterAcetylcholine (ACh)Acetylcholine (ACh)
Postsynaptic structurePostsynaptic membrane of next neuroneSarcolemma of muscle fibre
Receptor typeComplementary ACh receptor on postsynaptic membraneComplementary ACh receptor on sarcolemma
Can be inhibitory?Yes — can be excitatory or inhibitory depending on the neurotransmitterNo — always excitatory
Response generatedAP or EPSP in postsynaptic neuroneAP → muscle contraction
Enzyme presentAcetylcholinesteraseAcetylcholinesterase
Key Similarity
Both use ACh as neurotransmitter and both contain acetylcholinesterase to terminate the signal — making them both "cholinergic."
Predicting Drug Effects
AQA will give you an unfamiliar drug and its mode of action — you must predict and explain the synaptic effect. You do not need to memorise drug names.
Framework for Drug Questions
Identify which step in the 7-step mechanism the drug interferes with, then reason through the consequence:
Drug Mode of ActionEffect on SynapseBiological Consequence
Blocks voltage-gated Ca²⁺ channelsLess Ca²⁺ entry → fewer vesicle fusions → less ACh releasedReduced/no postsynaptic depolarisation
Blocks ACh receptors (competitive)ACh cannot bind → Na⁺ channels stay closedNo EPSP generated; no muscle contraction at NMJ
Inhibits acetylcholinesteraseACh not broken down → ACh accumulates in cleftProlonged/repeated stimulation of postsynaptic cell
Prevents vesicle fusion (e.g. botulinum toxin)ACh not released → no signal crosses cleftNo postsynaptic response; muscle paralysis at NMJ
Exam Technique
Always explain why — never just state the outcome. E.g. "ACh accumulates because acetylcholinesterase is inhibited, so receptors remain bound and Na⁺ channels stay open, causing prolonged depolarisation."
DEEP Chain: Synaptic Transmission
Use this structure when answering any extended response on synaptic transmission:
D
Define A synapse is a junction between two neurones across which impulses are transmitted chemically via neurotransmitters. At a cholinergic synapse, the neurotransmitter is acetylcholine (ACh).
E
Explain the Mechanism An AP at the presynaptic terminal opens voltage-gated Ca²⁺ channels → Ca²⁺ enters → synaptic vesicles fuse with the presynaptic membrane → ACh released by exocytosis → ACh diffuses across the cleft → binds to complementary receptors on the postsynaptic membrane → Na⁺ channels open → Na⁺ influx → depolarisation → EPSP generated. Acetylcholinesterase then hydrolyses ACh → choline + ethanoate; choline reabsorbed and ACh resynthesised.
E
Evidence / Example Synapses are unidirectional because vesicles are only presynaptic and receptors only postsynaptic. Summation (temporal: rapid successive impulses; spatial: multiple presynaptic neurones) allows subthreshold EPSPs to sum and reach threshold.
P
Practical / Quantitative At the NMJ, ACh binds to the sarcolemma → AP propagates via T-tubules → Ca²⁺ released from sarcoplasmic reticulum → muscle contraction. Drugs inhibiting acetylcholinesterase (e.g. nerve agents) cause ACh accumulation → continuous depolarisation → paralysis/convulsions.
Examiner Alerts
Error 1: Vesicles "move across"
Vesicles fuse with the presynaptic membrane and release ACh by exocytosis. Vesicles do NOT move across the synaptic cleft. ACh diffuses across — not the vesicles.
Error 2: Receptor location
ACh binds to receptors on the sarcolemma (at the NMJ) or the postsynaptic membrane. Saying "muscle" or "cell surface" without precision loses marks.
Error 3: Ca²⁺ at the NMJ
Ca²⁺ ions enter at the presynaptic terminal to trigger vesicle fusion. A separate Ca²⁺ release from the sarcoplasmic reticulum occurs later to trigger myofibril contraction. These are two different Ca²⁺ events — do not conflate them.
Error 4: Saying ACh "opens" Na⁺ channels directly
ACh binds to receptors which are linked to Na⁺ channels. It is the receptor binding that opens the channel — ACh does not directly open the channel itself.
Synoptic Links
🔗 Synoptic Link
Synapses → Muscle Contraction (6.06): The NMJ is the bridge between the nervous system and the musculoskeletal system. The AP generated at the sarcolemma links directly to the Ca²⁺ release from the sarcoplasmic reticulum and the sliding filament mechanism.
🔗 Synoptic Link
Exocytosis (2.04): ACh release by exocytosis involves vesicle fusion with the plasma membrane — the same membrane transport mechanism studied in Cells. Paper 3 synoptic questions frequently combine nervous system content with cell biology.
🔗 Synoptic Link
Protein structure (1.04): ACh receptors are integral membrane proteins — tertiary structure gives complementary binding site. Denaturation of receptors by extreme conditions would prevent ACh binding. Links to enzyme active site specificity (1.05).
🔗 Paper 3 Essay Trigger
Synaptic transmission frequently appears in synoptic essays on "The role of calcium ions in biological processes" — covering Ca²⁺ at the presynaptic terminal and Ca²⁺ from the sarcoplasmic reticulum in muscle contraction.
Practice Question
A student investigates the effect of a drug on a cholinergic synapse. The drug binds irreversibly to acetylcholinesterase and prevents it from functioning.
Explain the effect of this drug on synaptic transmission, and predict the likely physiological consequence at a neuromuscular junction. [5 marks]
D:
Acetylcholinesterase is the enzyme in the synaptic cleft that hydrolyses acetylcholine into choline and ethanoate, terminating the signal.
E:
If acetylcholinesterase is inhibited, ACh is not broken down and accumulates in the synaptic cleft. ACh continues to bind to receptors on the sarcolemma/postsynaptic membrane, so Na⁺ channels remain open. Continuous Na⁺ influx causes prolonged depolarisation — repeated EPSPs are generated without the normal termination step.
E:
At the NMJ, this would mean the muscle fibre receives a continuous signal to contract. APs would be repeatedly generated across the sarcolemma, triggering repeated Ca²⁺ release from the sarcoplasmic reticulum and sustained muscle contraction (tetanus/spasm).
P:
This mechanism is exploited by organophosphate nerve agents and some pesticides. In overdose, continuous stimulation of respiratory and skeletal muscles causes convulsions and respiratory failure. The irreversible nature means the effect persists until new enzyme is synthesised.
Summary
7-Step Cholinergic Synapse Sequence
StepEventKey Molecule
1AP arrives at presynaptic terminal—
2Voltage-gated Ca²⁺ channels openCa²⁺
3Vesicle fusion → ACh exocytosisACh, synaptic vesicles
4ACh diffuses across cleftACh
5ACh binds receptors → Na⁺ influx → EPSPNa⁺, AChR
6Acetylcholinesterase hydrolyses AChAChE, choline, ethanoate
7Choline reabsorbed → ACh resynthesised (ATP)ATP
Unidirectionality
Vesicles only presynaptic; receptors only postsynaptic.
NMJ
Always excitatory; ACh → sarcolemma → AP → T-tubules → Ca²⁺ from SR → contraction.
Exam Tip
The most common lost marks: (1) calling the muscle receptor location "muscle" not sarcolemma; (2) confusing temporal and spatial summation; (3) forgetting that ACh must be hydrolysed by acetylcholinesterase — this is always a mark point.
Next: Key Definitions