Abstract
The blocking effect of β-hungarotoxin (β-BuTX) isolated from the venom of Bungarus multicinctus on neuromuscular transmission in the rat isolated diaphragm was studied. No postsynaptic action on the membrane potential, action potential or the sensitivity to acetylcholine of the motor end-plate was observed. Since conduction in the phrenic nerve and its terminal also was unaffected, the action of β-BuTX seems to be confined exclusively to the presynaptic site. Although the binding of the toxin to action sites was almost complete within 20 minutes, it took more than 60 minutes for the inhibitory effect to appear. Shortly after application of the toxin, an increase in both frequency of miniature end-plate potentials and quantal content of end-plate potentials was observed. The onset of neuromuscular blockade was dependent on the stimulus frequency, being shorter at higher frequencies. Both Ca++-deficient and high Mg++ media antagonized the binding as well as the change after biniding which leads to the inhibitory effect. β-BuTX did not reduce the store of acetylcholine in the diaphragm even after complete neuromuscular blockade when the quantal content of end-plate potentials was markedly reduced. After neuromuscular blockade bursts of miniature end-plate potentials could be evoked by hypertonicity or high K+. It is concluded that the depression of the release of neurotransmitter by β-BuTX is not due to depletion of the store as previously postulated but is due to an inhibition of the mechanism for releasing neurotransmitter. The possibility of a causal link between an initial facilitation and the subsequent inhibition of transmitter release is discussed.
Footnotes
- Received May 9, 1972.
- Accepted September 30, 1972.
- © 1973 by The Williams & Wilkins Co.
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