Lambert-Eaton syndrome involves autoimmune attack on which presynaptic structure?

• A. Presynaptic voltage-gated calcium channels.
• B. Acetylcholine receptors.
• C. Dopamine receptors.
• D. Sodium channels in axon hillock.

Answer: (A)

Lambert-Eaton myasthenic syndrome is caused by autoantibodies that attack the presynaptic voltage-gated calcium channels at the neuromuscular junction. These channels normally open to allow calcium influx when a nerve impulse arrives, which triggers acetylcholine-containing vesicles to fuse with the presynaptic membrane and release ACh into the synaptic cleft. When these calcium channels are blocked, less acetylcholine is released, so the postsynaptic muscle receptors aren’t sufficiently stimulated, leading to weakness and autonomic symptoms.

This is different from attacks on acetylcholine receptors, which occur in myasthenia gravis and are postsynaptic. Dopamine receptors are CNS targets and not part of NMJ transmission, and sodium channels in the axon hillock are involved in initiating the action potential, not in triggering acetylcholine release at the NMJ.