Neuromuscular transmission failure in myasthenia gravis: decrement of safety factor and susceptibility of extraocular muscles

An appropriate density of acetylcholine receptors (AChRs) and Na + channels (NaChs) in the normal neuromuscular junction (NMJ) determines the magnitude of safety factor (SF) that guarantees fidelity of neuromuscular transmission. In myasthenia gravis (MG), an overall simplification of the postsynaptic folding secondary to NMJ destruction results in AChRs and NaChs depletion. Loss of AChRs and NaChs accounts, respectively, for 59% and 40% reduction of the SF at the endplate, which manifests as neuromuscular transmission failure. The extraocular muscles (EOM) have physiologically less developed postsynaptic folding, hence a lower baseline SF, which predisposes them to dysfunction in MG and development of fatigue during “high performance” eye movements, such as saccades. However, saccades in MG show stereotyped, conjugate initial components, similar to normal, which might reflect preserved neuromuscular transmission fidelity at the NMJ of the fast, pale global fibers, which have better developed postsynaptic folding than other extraocular fibers.