Mutual Antagonism between Botulinum Toxin and β-Bungarotoxin

Abstract

BOTH botulinum toxin^1,2 and β-bungarotoxin^3,4, isolated from the venom of Bungarus multicinctus, have been shown to block neuromuscular (NM) transmission by inhibition of the release mechanisms of the neurotransmitter. The inhibitory effect by either toxin is observed in the rat diaphragm only after a latent period, while the binding of both to the tissue seems to, be almost complete during the latent period^3–5. There seem to be two processes for the inhibitory effect, the binding of toxins to the tissue, and the subsequent changes leading to the irreversible inhibition of the release mechanism of neurotransmitter⁴. The time course of the paralysis is markedly accelerated by an increase of stimulus frequency and delayed by procedures or factors which depress the activity of release mechanism, such as deficiency of calcium, increase of magnesium or decreased rate of nerve stimulation^4–6. By contrast with botulinum toxin (ref. 2 and our unpublished data), β-bungarotoxin shows an initial facilitatory effect⁴, causing increases of the frequency of the spontaneous miniature end-plate potential and the quantal content of end-plate potential. Questions then arise as to whether or not they bind at a same site and act by a similar mechanism. We therefore studied the interaction between the two toxins in order to investigate the mechanism of the neurotransmitter release inhibition.