Induction of giant miniature end-plate potentials during blockade of neuromuscular transmission by textilotoxin.

Abstract

The present study investigated the action of textilotoxin, isolated from the venom of the Australian common brown snake Pseudonaja textilis, on neuromuscular transmission in isolated toad nerve-muscle preparations. Initial muscle twitch tension experiments revealed a triphasic pattern of changes in muscle tension and a irreversible binding action of textilotoxin (10 micrograms/ml) similar to other snake beta-neurotoxins. This was characterised by an initial depression of twitch tension, followed by a period of enhanced tension, eventually leading to a reduction in tension to complete neuromuscular blockade. These actions on muscle tension were investigated further by assessing the action of textilotoxin on end-plate potential amplitude (EPP). This revealed a similar triphasic alteration of the nerve-evoked release of acetylcholine from the motor nerve terminal. These actions on acetylcholine release were confirmed to be of a presynaptic origin since the modal amplitude of miniature end-plate potentials (MEPPs) was not reduced and in twitch tension experiments the muscle still contracted in response to direct muscle stimulation when nerve-evoked release was completely blocked. Interestingly dramatic effects were observed on the spontaneous release of acetylcholine, including an marked increase in MEPP frequency, a skewing of the MEPP amplitude frequency histogram to the right, and a resultant increase in the number of 'giant' MEPPs. These results indicate that textilotoxin causes a presynaptic blockade of neuromuscular transmission involving a disruption of the regulatory mechanism that controls acetylcholine release.