Myasthenia gravis
An autoimmune attack on the postsynaptic acetylcholine receptor at the neuromuscular junction reduces the safety margin for transmission, so muscle strength fails progressively with repeated use, fatigable weakness, because each successive nerve impulse recruits an ever smaller pool of intact receptors.
First principles
The defect is fewer receptors, not a failure to release acetylcholine
At a normal neuromuscular junction, each nerve impulse releases more acetylcholine than is strictly needed to trigger a muscle action potential, a reserve called the safety margin. In myasthenia gravis, autoantibodies, most often against the acetylcholine receptor itself or against MuSK, a protein needed to cluster receptors, reduce the number of functional postsynaptic receptors and can also directly damage the postsynaptic membrane, narrowing this safety margin. Presynaptic acetylcholine release is normal; the defect is purely on the receiving end.
Educational content pending clinical review. Not medical advice.