A 62-year-old male smoker presents with progressive proximal muscle weakness of six months, marked hyporeflexia, dry mouth and impotence. Strength improves noticeably after a few minutes of sustained handgrip exercise. Chest imaging reveals a hilar mass. The defect responsible for his weakness lies at which site of neuromuscular transmission?
- A Postsynaptic nicotinic acetylcholine receptors at the motor end plate
- B Acetylcholinesterase at the synaptic cleft
- C Presynaptic voltage-gated calcium channels required for acetylcholine release ✓
- D Voltage-gated sodium channels along the motor nerve terminal
Correct answer: C. Presynaptic voltage-gated calcium channels required for acetylcholine release
Explanation
This is Lambert-Eaton myasthenic syndrome, a paraneoplastic disorder usually associated with small cell lung carcinoma. Autoantibodies against presynaptic P/Q-type voltage-gated calcium channels reduce calcium-dependent acetylcholine release, so repetitive activity builds intraterminal calcium and transiently improves strength, the opposite of myasthenia gravis where postsynaptic receptors are attacked and exercise worsens fatigue. Acetylcholinesterase and nerve sodium channels are unaffected.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.