Neuromuscular junction

Junctio neuromuscularis

Also known as: NMJ, motor end plate, myoneural junction, end-plate, acetylcholine receptor

The chemical synapse between an α-motor neuron terminal and a skeletal muscle fibre. Acetylcholine acting on nicotinic receptors produces an end-plate potential that reliably triggers a muscle action potential.

Overview

Cleft width≈50 nm

ACh per vesicle (quantum)≈5,000–10,000 molecules

Safety factor≈3–5

NMJs per fibreusually 1

The motor axon loses its myelin near the fibre and branches into terminal boutons that lie in shallow gutters of the sarcolemma (the motor end plate). Terminal Schwann cells cap them. The presynaptic terminal contains mitochondria and ACh-filled synaptic vesicles, which dock at active zones next to voltage-gated P/Q-type Ca²⁺ channels. The synaptic cleft (≈50 nm) contains a basal lamina rich in acetylcholinesterase (AChE). The postsynaptic membrane is thrown into junctional folds. Nicotinic ACh receptors cluster at the crests of the folds, held in place by agrin–LRP4–MuSK signalling and rapsyn. Voltage-gated Na⁺ channels (Naᵥ1.4) are concentrated in the troughs.

Transmission: the action potential arrives and Ca²⁺ enters the terminal. Vesicles fuse through the SNARE complex (synaptobrevin, syntaxin, SNAP-25), releasing ≈100+ quanta, each containing ≈5,000–10,000 ACh molecules. ACh binds the two α-subunits of the nicotinic receptor (adult form α₁₂β₁δε), which opens a non-selective cation channel. Na⁺ entry produces an end-plate potential (EPP) far above threshold: a safety factor of ≈3–5. This fires an action potential that spreads in both directions along the fibre. AChE hydrolyses ACh into acetate and choline within about a millisecond, and choline is recycled. Each fibre usually has just one NMJ, located near the middle of the fibre.

Parts & subdivisions

Presynaptic terminal

Synaptic vesicles, active zones and P/Q-type voltage-gated Ca²⁺ channels.

Synaptic cleft

≈50 nm wide. Its basal lamina contains AChE, agrin and laminins.

Motor end plate

Postsynaptic sarcolemma with junctional folds. nAChRs sit at the crests and Naᵥ1.4 channels in the troughs.

Terminal Schwann cells

Cap the terminal and support maintenance and repair of the synapse.

Function

Transmits the motor command from nerve to muscle with a 1 : 1 relationship (every nerve impulse produces a muscle action potential)

Ends transmission rapidly through AChE, allowing high firing rates

Physiology

Spontaneous release of single quanta produces miniature end-plate potentials (≈0.5 mV). An evoked EPP of ≈50–75 mV comfortably exceeds threshold. Depolarising blockers (succinylcholine) cause fasciculations followed by phase I block. Non-depolarising blockers (rocuronium, vecuronium) compete with ACh and are reversed by neostigmine or sugammadex.

Clinical significance

Myasthenia gravis

Autoantibodies against nAChR or MuSK reduce the safety factor and cause fatigable weakness. Treated with AChE inhibitors (pyridostigmine), immunotherapy and thymectomy.

Lambert–Eaton myasthenic syndrome

Antibodies against presynaptic P/Q-type Ca²⁺ channels, often paraneoplastic with small-cell lung cancer. Proximal weakness improves after brief exercise (post-tetanic facilitation), with areflexia and autonomic symptoms.

Organophosphate poisoning and botulism

AChE inhibitors (organophosphate insecticides, nerve agents) cause a cholinergic crisis: muscarinic DUMBELS signs, fasciculations, then depolarising paralysis. Treat with atropine and pralidoxime. Botulinum toxin prevents ACh release and causes flaccid paralysis.