A patient with myasthenia gravis has an impaired neuromuscular junction. The safety factor of the NMJ refers to which concept, and how does it explain the characteristic fatigability?
- A The ratio of acetylcholine synthesis rate to breakdown rate, which falls during high-frequency stimulation
- B The number of active zone release sites minus the number of AChR, which determines postsynaptic sensitivity
- C The ratio of miniature end-plate potentials (MEPPs) to threshold depolarisation required for Na+ channel activation
- D The quantal content of each nerve impulse normally far exceeds the threshold required for muscle action potential; in MG, reduced end-plate potential amplitude falls below threshold with repetitive stimulation, causing decrement ✓
Explanation
The NMJ safety factor refers to the excess margin by which the end-plate potential (EPP) normally exceeds the threshold for muscle action potential generation. Normally, each nerve impulse releases ~100-200 quanta of ACh, producing an EPP of ~50-70 mV — far above the ~15-20 mV threshold needed to fire the muscle AP. In myasthenia gravis, anti-AChR antibodies reduce functional receptor density and cause complement-mediated junctional membrane damage. The EPP amplitude falls. During repetitive stimulation (high-frequency), physiological presynaptic rundown (vesicle depletion) further reduces quantal release; the already-reduced EPP falls below threshold, causing successive action potential failures — manifesting as progressive fatigability and the characteristic EMG decrement at 3 Hz stimulation.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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