Neuromuscular Junction
The synapse between a motor neuron and a muscle fibre where acetylcholine transmits the signal for muscle contraction. In myasthenia gravis, autoantibodies attack components of this junction. Zilucoplan protects the neuromuscular junction by inhibiting complement-mediated damage.
Technical Context
NMJ structure: presynaptic motor nerve terminal (containing ACh-loaded synaptic vesicles, voltage-gated calcium channels) → synaptic cleft (~50nm, containing AChE) → postsynaptic muscle membrane (endplate, containing densely packed nicotinic AChRs, approximately 10,000/μm²). Transmission: action potential → Ca²⁺ influx through presynaptic VGCCs → SNARE-mediated vesicle fusion → ACh release (approximately 200 quanta per impulse) → ACh binds nicotinic AChR (two ACh molecules per receptor) → channel opens → Na⁺ influx → endplate potential (EPP) → if EPP exceeds threshold, muscle action potential → excitation-contraction coupling → muscle contraction. Safety factor: the EPP normally exceeds threshold by 2-3× (safety margin). In MG, autoantibody-mediated AChR loss reduces the safety factor → some endplates fail to reach threshold → muscle weakness. Zilucoplan prevents complement-mediated NMJ damage, preserving the remaining AChR population.