Comparison of the presynaptic actions of botulinum toxin and β-bungarotoxin on neuromuscular transmission
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Comparison was made between the presynaptic actions of type A botulinum toxin (BoTX) and β-bungarotoxin (β-BuTX) on isolated nerve-muscle preparations. On the mouse and rat diaphragms, BoTX is about 100 and 10 times more potent than β-BuTX, respectively, whereas on the chick biventer cervicis muscle, β-BuTX is 3–10 times more potent. The paralytic actions of both toxins are preceded by latency, antagonized by high concentrations of calcium or magnesium and by deficiency of calcium, accelerated by high frequencies of nerve stimulation and retarded by decrease of temperature. The paralytic actions of BoTX as well as β-BuTX appear to take place in two processes: first, binding with their respective target sites and second, the inhibitory changes of the target macromolecule of the nerve terminals leading to failure of transmitter release. The latter process is not reversed by washing but is retarded greatly by low calcium, high magnesium or low temperature. Binding of β-BuTX is faster than that of BoTX.
Miniature end-plate potentials of unreduced amplitude could be recorded in junctions blocked by either toxin. End-plate potentials were depressed and the successive decline of their amplitude during train of pulses was abolished by both toxins.
In contrast to the initial facilitatory actions after β-BuTX, BoTX has no sign of facilitation such as increase of the frequency of miniature end-plate potential, restoration of neuromuscular transmission, increase of quantal content of end-plate potential and occurrence of spontaneous fasciculations in low calcium media. Another difference between the two toxins is the typical Wedensky inhibition on repetitive stimulation and post-tetanic potentiation in β-BuTX paralysed muscles. By contrast, after BoTX, sustained contraction without post-tetanic potentiation was observed.
The two toxins show a mutual antagonism especially when β-BuTX is added before or simultaneously with BoTX. The action of the latter was completely antagonized in the presence of β-BuTX. Once it is bound to the target site, however, BoTX seems not to be antagonized by β-BuTX. On the other hand, BoTX appears to be able to retard the effect of bound β-BuTX.
Key wordsBotulinum Toxin β-Bungarotoxin Presynaptic Actions Low Calcium High Magnesium Effect of Temperature
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