Which statement best describes the mechanism by which botulinum toxin affects neuromuscular transmission and the resulting muscle state?

• A. It inhibits acetylcholine release at the neuromuscular junction by cleaving SNARE proteins, causing spastic paralysis.
• B. It inhibits acetylcholine release at the neuromuscular junction by cleaving SNARE proteins, causing flaccid paralysis.
• C. It enhances acetylcholine release, causing rigid paralysis.
• D. It blocks calcium channels at the neuromuscular junction, causing tremors.

Answer: (B)

Neuromuscular transmission hinges on acetylcholine being released from the presynaptic terminal. Botulinum toxin blocks this release by proteolytically cleaving SNARE proteins (such as SNAP-25, syntaxin, or synaptobrevin) that are essential for vesicle fusion with the presynaptic membrane. Without SNARE-mediated fusion, acetylcholine-containing vesicles cannot fuse and release ACh into the synaptic cleft. Consequently, the motor endplate receives little stimulation, the end-plate potential fails to trigger muscle fiber depolarization, and the muscle cannot contract. This produces flaccid paralysis—reduced muscle tone and weakness. This differs from toxins that cause spastic or rigid states, or those that act by blocking calcium channels or increasing transmitter release, which would produce different effects such as tremors or sustained contractions.