Blockade of acetylcholine receptors is another form of autoimmune attack. Antibodies from patients with MG have been shown to block the acetylcholine binding sites, which prevents acetylcholine from binding to its receptor and opening the ion channel. It is probable that the antibodies bind near the acetylcholine binding site rather than directly on it, because the acetylcholine binding site is so small. In this case the antibodies would prevent acetylcholine from binding at the receptor by "getting in the way" of the acetylcholine molecule as it moves towards its receptor; this effect is known as steric hinderance.
In myasthenic patients the neuromuscular junction has decreased numbers of acetylcholine receptors, a wider synaptic cleft, and simplified synaptic folds. These changes account for the clinical features of myasthenia gravis. Decreased numbers of acetylcholine receptors result in fewer interactions between acetylcholine and it's receptors, leading to decreased activation of action potentials. When the transmission of action potentials decreases, the power of the muscle's contraction is reduced, causing weakness. During repeated nerve stimulation the amount of acetylcholine normally declines, or runs down. In myasthenia gravis, this run down occurs more rapidly due to a decrease of receptors in myasthenic junctions, causing muscular fatigability. The wider synaptic cleft and simplified synaptic folds also work to decrease the number of interactions between acetylcholine and acetylcholine receptors.
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