The Neuromuscular Junction To understand myasthenia, it helps to understand how the neuromuscular junction should work. 1. To make any muscle move a signal has to be sent from the brain, down the nerve to the muscle. Mostly we are totally unaware that this is happening, especially in the muscles that help us to breathe and swallow. 2. When the signal reaches the end of the nerve it causes a special chemical called acetylcholine (ACh) to be released from the nerve. The ACh travels across the gap between the nerve and the muscle and binds to the acetylcholine receptors (AChR) which are clustered by molecules called RAPSYN on the muscle. 3. The AChR is a channel that is normally closed but when the ACh binds to it following a signal, it opens for a short time to let in ions. It is this influx of ions that causes the muscle to work. After the process, any ACh left over is broken down by the acetylcholine-esterase (AChE), which is held in the gap between the nerve and the muscle by a protein called COLQ. The ACh is then recycled by an enzyme called ChAT. For all of this to happen, the AChRs need to be clustered in its correct position to receive the ACh. This is achieved by a number of different proteins (including DOK-7 and RAPSYN). Interference in any of these processes can prevent the muscles from working properly and cause weakness.