A novel peptide toxin from Trimeresurus wagleri acts pre- and post-synaptically to block transmission at the rat neuromuscular junction.

The neuromuscular effects of a peptide toxin (peptide I) from venom of Trimeresurus wagleri were investigated using the rat extensor digitorum longus muscle/peroneal nerve preparation. Sub-micromolar concentrations depressed endplate currents (EPCs) produced in response to nerve stimulation. Since quantal content of EPCs was not altered, it appears that the site of action is post-synaptic. However, higher concentrations (1.4-2.9 microM) also inhibited spontaneous release of transmitter. Nerve stimulation in the presence of peptide I caused 'rundown' of EPC amplitude, evidence that the peptide acts pre-synaptically to interfere with transmitter release. Recovery from this effect occurred within 3-5 min. of washing, but EPC amplitude took 20-30 min. to recover. The dual action of this peptide makes it unusual amongst naturally-occurring toxins, and these data suggest that further investigation of the peptide (and its analogues) could yield new information about neurotransmitter release.