The acquired form of myasthenia gravis is an immune-mediated disease caused by the production of antibodies directed against the proteins of acetylcholine receptors. These antibodies, mainly Ig G, cause accelerated breakdown of the receptors as well as blocking the acetylcholine binding sites. The result is severely reduced numbers of effective acetylcholine receptors in each neuromuscular junction. These antibodies also cause morphological changes in the neuromuscular junction, such as reduced folding of the postsynaptic membrane and a wider gap in the neuromuscular junction between the nerve and the muscle.

In a normal neuromuscular junction, acetylcholine effectively binds to the acetylcholine receptors which causes cation channels to open and produce successful muscle action potentials which stimulate muscle contraction. In animals with acquired myasthenia gravis, the nerves are functioning correctly and the normal amounts of acetylcholine are released, but the acetylcholine has troubles binding to its receptors. This may be due to lack of receptors from degradation or lack of available receptors that do not have antibodies already attached. If the amount of binding between acetylcholine and its receptors fall low, many muscle fibers will not have action potentials and therefore not contract and muscle weakness is produced. One of the main signs of acquired myasthenia gravis is progressive muscle weakness with exercise.

The reason muscle weakness gets worse with exercise is because with each repeating nerve impulse the amount of acetylcholine released usually declines. In this situation, not only is there a lack of receptors, there is also a decreasing amount of acetylcholine which decrease the chances even more of having acetylcholine binding to its receptors. Without binding of acetylcholine to its receptors there is no muscle action potential or muscle contraction.

Congenital Form of Myasthenia Gravis

The congenital form of myasthenia gravis is inherited as an autosomal recessive trait. The disease results from structural and functional abnormalities of nicotinic acetylcholine receptors. These abnormalities lead to insufficient amounts of the nicotinic acetylcholine receptors that function properly. Without sufficient numbers of functional nicotinic acetylcholine receptors, a muscle action potential cannot be triggered, and muscle contraction will not occur.

The Nerve Impulse (Action Potential)

Organisms respond to external stimuli. If the stimulus is stong enough, a nerve impulse occurs. The nerve impulse is an all-or-none event which depolarizes the membrane of the synaptic terminal of a nerve cell. The depolarization causes an increase in the calcium ion concentration. The calcium rushes into the nerve cell and causes synaptic vesicles, which contain the neurotransmitter acetylcholine, to fuse with the presynaptic membrane of the nerve and release the acetylcholine into the synaptic cleft. The synaptic cleft is the space that separates the presynaptic cell (nerve cell) from the postsynaptic cell (muscle cell) and is the location where the two cells communicate. When the synaptic cleft separates a nerve cell from a muscle cell it is referred to a neuromuscular junction. The acetylcholine then diffuses across the synaptic cleft to the acetylcholine receptors on the postsynaptic membrane of the muscle cell. The binding of acetylcholine to the acetylcholine receptors on the postsynaptic cell (muscle cell) triggers ion channels on the postsynaptic cell to open. The opening of these ion channels on the postsynaptic membrane of the muscle cell then stimulates the muscle cell to contract.