Interactions between Heavy Metal Chelators and Botulinum Neurotoxins at the MouseNeuromuscular Junction

摘要

Interactions between heavy metal chelators and botulinum neurotoxins at the mouseneuromuscular junction. Toxicon 33, 539-549, 1995. Exposure of isolated mouse hemidiaphragms to botulinum neurotoxins, 0.1 nM BoNT-A or BoNT-B, at 360C reduced nerve-elicited peak isometric twitch tension to 50% of control values at 55 min (BoNT-A) to 68 min (BoNT-B) after application. Either coincubation of BoNT with the heavy metal chelator TPEN, preincubation with TPEN followed by BoNT, or application of TPEN after BoNT but before neuromuscular block, delayed the onset of muscle failure in a dose-dependent manner by up to five-fold. TPEN doses between 2 and 10 u M were required to antagonize significantly the muscle block produced by BoNT, and the delay in onset was maximal between 10 and 50 uM TPEN.