Toxin Blockade Research Articles

Ionic requirements for the neuromuscular blocking action of botulinum toxin: Implications with regard to synaptic transmission

The neuromuscular blocking action of botulinum toxin is shown to be both temperature ( Q 10 $ ̄ 2.36; E a − 15.5 × 10 4 cal/mol)- and concentration (paralysis time ∼- K/ 4 √dose)-dependent when tested in vitro. Furthermore, neuromuscular blockade by the toxin develops only when Ca ++ is present in the bathing medium. The Ca ++ dependence of botulinum toxin is not related to tissue binding or co-factors. Instead, the release of acetylcholine appears to be necessary for toxin blockade to develop, and Ca ++ is necessary to permit acetylcholine release. Conditions that facilitate acetylcholine release (K + depolarization, hyperosmolarity) augment paralysis; conditions that impede acetylcholine release (omission of Ca ++, high Mg ++) hinder paralysis. Only the acetylcholine releasing process, and not the nerve depolarization-repolarization cycle, is necessary for toxin-induced blockade.