Neuromuscular junction (NMJ)

The neuromuscular junction (NMJ) is a specialised synapse between motor neurones and skeletal muscle, which enables nervous control of skeletal muscle contraction. At the NMJ, the neurone and skeletal membrane are brought into close contact by folding and the outside of the neurone is held in place by a Schwann cell. Anatomically, a collection of neuromuscular junctions form a motor end plate.

At the NMJ action potentials in the motor neurone cause depo­larisation of the presynaptic terminal (bouton), which leads to the opening of voltage-operated (gated) Ca²⁺ channels and the influx of Ca²⁺ ions. The influx of Ca²⁺ ions then stimulates the exocytosis of synaptic vesicles containing the neurotransmitter acetylcholine (ACh) (Figure 22.1).

When released, ACh diffuses across the synaptic cleft (typically 50 nm) and stimulates postsynaptic ionotropic nicotinic receptors. The nicotinic acetylcholine receptor (nAChR) is an ion-channel complex of five transmembraneous subunits (α₂, β, δ, γ) and opens on activation by ACh. The open ion-channel complex is permeable to both Na⁺ (influx) and K⁺ (efflux), and following activation there is transient cellular depolarisation, which leads to a miniature end plate potential (mEPP) of typically 0.4 mV. The vesicles of ACh are of a relatively consistent size and so the transmission is quantal, with packages of excitation leading to steps in excitation. The mEPPs generated at the NMJ summate to form excitatory post-synaptic potentials (EPPs) and once threshold is reached lead to actions potential via voltage-operated Na⁺ channels (sensitive to tetrodotoxin), which are propagated across the skeletal muscle by spreading depolarisation. The depolarisation of the skeletal muscle is coupled (via the T-tubular system) to Ca²⁺ release from the intracellular sarcoplasmic reticulum stores and the increase in intracellular Ca²⁺ leads to contraction of the skeletal muscle (Figures 22.1 and 22.2).

The actions of ACh (and therefore the signal for contraction) are terminated by acetylcholinesterase (AChE), which breaks down ACh into acetate and choline. The choline is then recycled by reuptake by the presynaptic terminal. The reuptake mechanism can be blocked by hemicholinium.