A 56-year-old man sees a specialist because of weakness in his legs that improves over the course of the day or with exercise. Extracellular electrical recordings from a single skeletal muscle fibre reveal normal miniature end-plate potentials. Low-frequency electrical stimulation of the motor neuron, however, elicits an abnormally small depolarization of the muscle fibres. The amplitude of the depolarization is increased after exercise. 83. Based on these findings, which of the following is the MOST likely cause of this patient’s leg weakness? A. Acetylcholinesterase deficiency B. Blockade of postsynaptic acetylcholine receptors C. Impaired presynaptic voltage-sensitive Ca2+ influx D. Inhibition of Ca2+ re-uptake into the sarcoplasmic reticulum E. Reduced acetylcholine synthesis 84. The molecular mechanism underlying these symptoms is MOST likely to involve which drug target? A. Receptors B. Ion channels C. Enzymes D. Tubulins E. Carrier molecules 85. The musculoskeletal condition above can be managed by which of the following drug agents? A. Ion channel modulators B. Receptor agonists C. Carrier molecules inhibitors D. Receptor antagonists E. Enzyme inhibitors
Question
A 56-year-old man sees a specialist because of weakness in his legs that improves over the course of the day or with exercise. Extracellular electrical recordings from a single skeletal muscle fibre reveal normal miniature end-plate potentials. Low-frequency electrical stimulation of the motor neuron, however, elicits an abnormally small depolarization of the muscle fibres. The amplitude of the depolarization is increased after exercise. 83. Based on these findings, which of the following is the MOST likely cause of this patient’s leg weakness? A. Acetylcholinesterase deficiency B. Blockade of postsynaptic acetylcholine receptors C. Impaired presynaptic voltage-sensitive Ca2+ influx D. Inhibition of Ca2+ re-uptake into the sarcoplasmic reticulum E. Reduced acetylcholine synthesis 84. The molecular mechanism underlying these symptoms is MOST likely to involve which drug target? A. Receptors B. Ion channels C. Enzymes D. Tubulins E. Carrier molecules 85. The musculoskeletal condition above can be managed by which of the following drug agents? A. Ion channel modulators B. Receptor agonists C. Carrier molecules inhibitors D. Receptor antagonists E. Enzyme inhibitors
Solution
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The most likely cause of this patient's leg weakness is B. Blockade of postsynaptic acetylcholine receptors. This is suggested by the fact that the patient's muscle fibers show an abnormally small depolarization in response to low-frequency electrical stimulation of the motor neuron, but the amplitude of the depolarization increases after exercise. This is consistent with a condition known as myasthenia gravis, which is caused by an autoimmune attack on the acetylcholine receptors at the neuromuscular junction, leading to their blockade and a reduction in the number of functional receptors.
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The molecular mechanism underlying these symptoms is most likely to involve A. Receptors. In this case, the acetylcholine receptors at the neuromuscular junction are the primary targets.
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The musculoskeletal condition above can be managed by B. Receptor agonists. These drugs can mimic the action of acetylcholine and stimulate the receptors, thereby improving muscle strength. An example of such a drug is pyridostigmine, which is often used in the treatment of myasthenia gravis.
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