Figure 1. Assessing neuromuscular transmission.

( A) Healthy neuromuscular transmission. The nerve terminal can release the contents of each vesicle (quanta) of acetylcholine by exocytosis. Spontaneous release of single quanta of acetylcholine activates the intrinsic cation channels of acetylcholine receptors (AChRs) in the postsynaptic membrane to produce a small, transient depolarisation called a miniature endplate potential (mEPP). The nerve action potential opens voltage-gated calcium channels (VGCCs) and triggers exocytosis of many quanta of acetylcholine, simultaneously producing the (much larger) EPP. In healthy individuals, the amplitude of the EPP is more than enough to reach the threshold required to activate the postsynaptic voltage-gated sodium channels (VGNaCs) and generate a muscle action potential. ( B) The myasthenia gravis neuromuscular junction. AChR antibodies (mainly immunoglobulin [Ig]G1) activate complement, resulting in membrane attack complex-mediated damage to the post-junctional membrane architecture. The postsynaptic AChR numbers are depleted by divalent antibodies inducing AChR internalisation. The loss of AChRs results in smaller mEPP and EPP amplitudes. The EPP may not reach threshold, especially when the nerve is repetitively activated. Abbreviations: AChE, acetylcholinesterase