Impact of α-bungarotoxin on transmitter release at the neuromuscular junction of the rat

Abstract

The drug, α-bungarotoxin (BTX) is believed to be a ‘pure’ nicotinic antagonist. Hence, use of this drug should avoid the secondary actions associated with other nicotinic antagonists. The hypothesis that the motor nerve terminal responds to the presence of acetylcholine (ACh) by releasing less transmitter was tested by examining the effects of BTX on end-plate potentials (EPPs), miniature end-plate potentials (MEPPs), and quantal release at the rat diaphragm neuromuscular junction. Analysis of EPP and MEPP amplitudes and quantal release demonstrate that BTX significantly increases transmitter release at the onset of tetanic stimulation (50 Hz). Like other nicotinic antagonists, BTX was not able to sustain enhanced quantal release during a brief train of 40 stimuli and resulted in greater decline in EPP amplitude during tetanic stimulation. The data suggests that negative feedback regulation by presynaptic autoreceptors only serves a functional role at the onset of stimulation and that other factors such as transmitter supply or adenosine regulation may serve to dominate transmitter release during maintained tetanic stimulation.