How does the neuromuscular junction work?
The neuromuscular junction is the connection between a motor nerve and muscle fiber.
The activated motor nerve triggers the release of acetylcholine (ACh), which then diffuses across the neuromuscular junction to the muscle (post-synaptic) membrane, binds to any available acetylcholine receptor (AChR), which then in turn activates the muscle fiber, ultimately leading to a motor contractions and a volitional movement.
What happens in myasthenia?
Some of these antibodies simply block the receptor’s binding sites so that ACh cannot activate the muscle membrane:
Other antibodies link the receptors together:
Which then leads to internalization of the receptors (endocytosis) and simplification of the post-synaptic membrane:
The end result is that the post synaptic membrane becomes simplified and devoid of working AChr, so there are little or no available binding sites for the released ACh to bind to:
Excess ACh is removed from the synaptic cleft by the enzyme acetylcholinesterase (AChE), which breaks it down into inactive constituents.
So, you can think of MG like a game of musical chairs, when some of the chairs have been taken away, and there some of the acetylcholine can’t find a place to sit down before it is gobbled up by the AChE.
You can tip the odds more in favor of facilitating neuromusucular transmission by inhibiting AChE, allowing ACh to stick around longer, making it more likely to find an available AChR to bond to, rather like waiting longer to remove the chairs in musical chairs.
Dr Mary Walker first uses physostigmine in MG
The Tensilon Test
We do still (rarely) use injectable AChEIs like prostigmine (neostigmine) for managing MG.
The oral AChEI pyridostigmine or Mestinon is now widely prescribed for symptomatic treatment of MG