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MCAT

Unit 2: Lesson 3

Foundation 3: Organ Systems

Repetitive nerve stimulation in Myasthenia gravis patients

Problem

The neuromuscular junction is a special synapse that utilizes the neurotransmitter acetylcholine (Ach) to stimulate muscle contraction. After a signal is transmitted through the neuromuscular junction, an enzyme known as acetylcholinesterase degrades Ach to prevent sustained muscle contraction.
Figure 1: The mechanism of signaling at the neuromuscular junction via the neurotransmitter acetylcholine. Adapted from: Capek, P, Dickerson TJ. (2010). Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection. Toxins (Basel). (CC - BY)
Myasthenia gravis is a disease that affects the neuromuscular junction. It is caused by autoantibodies (anti-AchR) that competitively inhibit the acetylcholine receptor (AchR) on the motor end plate. Antibody binding results in the closure of the ligand-gated channels, thus preventing signal transduction. The hallmark finding in individuals with myasthenia gravis is fatigable muscle weakness, particularly in the muscles of the eyelids.
Repetitive nerve stimulation (RNS) electromyography is a test used to diagnose myasthenia gravis. The test measures the amplitude of action potentials while a muscle is repetitively stimulated 5 times at a frequency of 2 to 5 Hz. The amplitudes of the first, fourth, and fifth stimuli are then recorded. A reproducible decrease in the amplitude of the signal by ≥10% between the first stimulus and the fourth or fifth stimuli is considered diagnostic for myasthenia gravis.
Acetylcholinesterase inhibitors (neostigmine and pyridostigmine) are FDA approved for the treatment of myasthenia gravis. These drugs competitively inhibit the action of acetylcholinesterase and therefore prevent the degradation of Ach in the synaptic cleft. This effectively increases the amount of Ach available in the neuromuscular junction to compete with anti-AchR for binding of AchR.
A researcher is studying the effect of neostigmine and pyridostigmine on individuals with myasthenia gravis. To do so, he conducts a study on individuals previously diagnosed with myasthenia gravis. In his experiment 300 subjects are randomly assigned to 3 treatment groups (placebo, neostigmine, or pyridostigmine). The subjects receive a single treatment dose and then undergo immediate RNS testing and subsequent testing at 30 minute intervals for 150 minutes. The effectiveness of each drug is measured by the improvement of neuromuscular transmission, as measured by a negative RNS test for myasthenia gravis (Figure 2).
Figure 2: Effectiveness of acetylcholinesterase inhibitors versus placebo in treatment of myasthenia gravis
Which of the following types of neuron describes the presynaptic neuron in figure 1?
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