Q2
LONG ANSWER
10M
★ High-yield
Describe the structure of the neuromuscular junction and the steps of neuromuscular transmission. Add a note on the drugs acting on it.
Definition
Neuromuscular junction (motor end plate) = the specialised synapse between the terminal branch of a motor nerve fibre and the membrane of a skeletal muscle fibre.
Structure
- Presynaptic terminal — unmyelinated axon ending; contains synaptic vesicles of acetylcholine (about 10,000 molecules per vesicle) and many mitochondria
- Synaptic cleft — 20–50 nm wide; contains acetylcholinesterase in the basal lamina
- Postsynaptic membrane (end plate) — thrown into junctional folds to ↑ surface area; bears nicotinic (NM) receptors at the crests
Steps of Neuromuscular Transmission
Nerve action potential reaches terminal → Voltage-gated Ca2+ channels open → Ca2+ influx → vesicles fuse with membrane → ACh released by exocytosis (about 125 vesicles) → ACh binds nicotinic receptor → Na+ influx → End Plate Potential → EPP reaches threshold → Muscle action potential → contraction
End Plate Potential (epp)
| Feature | EPP | Action potential |
|---|---|---|
| Nature | Graded (local) | All-or-none |
| Propagated | No — decays with distance | Yes |
| Summation | Yes | No |
| Refractory period | Absent | Present |
| Ion | Na+ in, K+ out together | Na+ then K+ sequentially |
- MEPP (miniature end plate potential) — 0.5 mV; produced by spontaneous release of a single quantum (one vesicle)
- Normal EPP is about 3–4× larger than needed to reach threshold — the safety factor of transmission
Fate of Acetylcholine
ACh in cleft → Acetylcholinesterase → Choline + acetate → Choline reuptake into nerve terminal (rate-limiting) → Recombined with acetyl CoA by choline acetyltransferase → ACh resynthesised
- Hydrolysis is complete in 1 millisecond → permits rapid repetitive transmission
Quantal Release of Acetylcholine
- Quantum = the contents of one synaptic vesicle, about 10,000 ACh molecules
- At rest, single quanta are released spontaneously → MEPPs of 0.5 mV
- One nerve impulse releases about 125–300 quanta simultaneously → a full EPP of 50–75 mV
- Release is strictly Ca2+ dependent — no Ca2+, no release
- Mg2+ competitively inhibits Ca2+ → hypermagnesaemia causes weakness
Properties of Neuromuscular Transmission
- One-way (unidirectional) conduction
- Synaptic delay — 0.5–1 ms, mainly the time for Ca2+-triggered exocytosis
- Fatigue on prolonged high-frequency stimulation — ACh stores deplete
- Susceptible to hypoxia and drugs
- 1:1 transmission — each nerve impulse normally produces one muscle impulse
Drugs and Toxins Acting at the NMJ
| Agent | Site | Effect |
|---|---|---|
| D-Tubocurarine | Nicotinic receptor | Competitive (non-depolarising) block → flaccid paralysis; reversed by neostigmine |
| Succinylcholine | Nicotinic receptor | Depolarising block → fasciculations then paralysis; not reversed by neostigmine |
| Neostigmine, physostigmine | Cholinesterase | Inhibit breakdown → ↑ ACh |
| Organophosphates | Cholinesterase | Irreversible inhibition → cholinergic crisis; treated with atropine + pralidoxime |
| Botulinum toxin | Presynaptic | Blocks ACh release (cleaves snare proteins) → flaccid paralysis |
| Black widow spider venom | Presynaptic | Massive ACh release → spasm |
| Hemicholinium | Presynaptic | Blocks choline reuptake |
Comparison — Neuromuscular Junction VS Neuronal Synapse
| Feature | Neuromuscular junction | Neuronal synapse |
|---|---|---|
| Transmitter | Always ACh | Many |
| Effect | Always excitatory | Excitatory or inhibitory |
| Convergence | One nerve to one fibre | Many presynaptic on one neurone |
| Summation needed | No — one impulse suffices | Yes — temporal and spatial |
| Safety factor | High (3–4×) | Low |
| Fatigue | Slow | Rapid |
Applied Aspects
- Myasthenia gravis — autoantibodies against nicotinic receptors → ↓ receptor number → fatigable weakness; improves with neostigmine
- Lambert–Eaton syndrome — antibodies against presynaptic Ca2+ channels → ↓ ACh release; strength improves with repeated activity (opposite of myasthenia)
- Tetanus toxin — blocks inhibitory glycine release in the cord → spastic paralysis (contrast with botulinum)
- Organophosphate poisoning — sludge features (salivation, lacrimation, urination, defaecation, GI upset, emesis) with muscle fasciculation; treat with atropine and pralidoxime before ageing of the enzyme occurs
- Aminoglycosides → ↓ ACh release → may unmask or worsen myasthenia
All questions in Nerve & Muscle Physiology
- Q1Define action potential. Describe its phases and ionic basis. Add a note on the refractory period. ★
- Q2Describe the structure of the neuromuscular junction and the steps of neuromuscular transmission. Add a note on the drugs acting on it. ★
- Q3Describe the sliding filament mechanism of skeletal muscle contraction. Explain excitation–contraction coupling and the role of calcium. ★
- Q4Classify nerve fibres. Describe the mechanism of impulse conduction and compare saltatory with continuous conduction. Add a note on nerve degeneration and regeneration. ★
- Q5Compare the structure and properties of skeletal, cardiac and smooth muscle. Describe the mechanism of smooth muscle contraction. ★
- SN1Write a short note on myasthenia gravis. ★
- SN2Write a short note on rigor mortis. ★
- SN3Define motor unit. Describe the innervation ratio and the size principle. ★
- SN4Differentiate between isotonic and isometric contraction.
- SN5Describe the changes following section of a peripheral nerve. Add a note on regeneration. ★
- SN6Describe the length–tension relationship of skeletal muscle and give its significance.
- SN7Write a short note on muscle fatigue. Add a note on oxygen debt.