Neurons, synapses and neurotransmitters
Diperkenalkan| English | Makna |
|---|---|
| voltage-gated calcium channels | voltage-gated calcium channels |
| ionotropic receptors | ionotropic receptors |
| metabotropic receptors | metabotropic receptors |
| neuromuscular junction/ˌnjuːrəˈmʌskjʊlə ˈdʒʌŋkʃn/ | The specialised synapse through which a motor neurone signals to a muscle fibre. |
| acetylcholinesterase | acetylcholinesterase |
One junction, three poisons
- Botulinum toxin, the curare on hunters' darts and the tetanus toxin all paralyse by acting at synapses, but at different steps, and one of them makes muscles stiff instead of floppy.
- The synapse is where the nervous system decides, and where most nerve drugs and toxins act.
Six steps across the gap
- An action potential reaches the terminal, voltage-gated calcium channels 电压门控钙通道 open, and Ca²⁺ entry makes vesicles fuse (SNARE proteins) and release transmitter.
- The transmitter crosses the cleft, binds receptors, and is then removed by reuptake or broken down.
Put the steps of synaptic transmission in order.
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Calcium entry is the trigger that links the electrical signal to chemical release.
Fast and slow receptors
- Ionotropic receptors 离子型受体 are channels: they open within milliseconds (nicotinic ACh, GABA-A, glutamate AMPA and NMDA).
- Metabotropic receptors 代谢型受体 work through G proteins, over hundreds of milliseconds to seconds (muscarinic, adrenergic, most dopamine and serotonin receptors).
Which receptor acts within milliseconds?
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Ionotropic receptors are channels and open at once; the others work through G proteins.
The receptor sets the sign
- ACh excites skeletal muscle through nicotinic receptors but slows the heart through M2 receptors: the receptor, not the transmitter, decides.
- In the adult brain glutamate acts almost only on excitatory receptors, and GABA and glycine on inhibitory ones.
ACh always excites the cell it acts on.
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It excites skeletal muscle through nicotinic receptors but slows the heart through M2 receptors.
The safety factor
- At the neuromuscular junction 神经肌肉接头 one impulse releases about 50–300 vesicles. The resulting potential is 3–5 times larger than needed to fire the muscle.
- So weakness appears only when about 70–80% of receptors are blocked, as in myasthenia gravis.
Why does losing some ACh receptors not cause weakness at first?
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The safety factor hides receptor loss until about 70–80% of receptors are blocked.
Ending the signal
- Acetylcholinesterase 乙酰胆碱酯酶 breaks ACh down in the cleft within milliseconds. Monoamines such as serotonin are taken back into the terminal by transporters.
- SSRIs block the serotonin transporter, so serotonin stays longer in the cleft; they do not change how much is made.
How do SSRIs raise serotonin in the synaptic cleft?
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Blocking reuptake leaves serotonin in the cleft for longer.
Worked example: counting molecules
- One vesicle holds about 5000–10 000 ACh molecules, and one impulse releases 50–300 vesicles.
- Range: $50 \times 5000 = 2.5 \times 10^5$ to $300 \times 10\,000 = 3 \times 10^6$ molecules per impulse, far more than threshold needs.
One impulse releases 200 vesicles, each with 7000 ACh molecules. How many million molecules is that?
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200 × 7000 = 1 400 000 = 1.4 million.
Worked example: three toxins, three steps
- Botulinum toxin cuts SNARE proteins, so no ACh is released: floppy paralysis. Curare blocks the nicotinic receptor: floppy paralysis with normal release.
- Tetanus toxin travels to the spinal cord and blocks release from inhibitory interneurons: excitation is unopposed, and muscles go into spasm. Where a toxin acts predicts the kind of paralysis.
Match each agent to what it does.
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The site of action predicts the effect.
Three common slips
- "ACh is excitatory." Nicotinic receptors excite muscle; M2 receptors slow the heart.
- "SSRIs make more serotonin." They block its reuptake.
- Forgetting calcium. Without Ca²⁺ entry there is no release, however depolarised the terminal.
Recap
- AP → Ca²⁺ entry → vesicle fusion → cleft → receptor → removal.
- Ionotropic receptors are fast channels; metabotropic receptors are slower G-protein receptors; the receptor sets the sign.
- The NMJ has a 3–5 times safety factor; blocking release or receptors gives floppy paralysis, blocking inhibition gives spasm.