Dissociation of the end-plate potential run-down and the tetanic fade from the postsynaptic inhibition of acetylcholine receptor by α-neurotoxins

Abstract

The effects of so-called postsynaptic snake α-neurotoxins (α-bungarotoxin, cobratoxin, erabutoxin b) on the wanings of tetanic contraction (tetanic fade) and the run-down of end-plate potentials during stimulation at 100 Hz were studied, respectively, in intact and cut mouse phrenic nerve-diaphragm preparations. No tetanic fade was evident with high concentrations of toxins until the complete failure of contractile response whereas the tetanic fade was evident after prolonged incubation with lower concentrations of toxins. The proportion of junctions exhibiting end-plate potential run-down increased progressively during toxin incubation. However, depression of end-plate potential amplitude by the toxins was not necessarily accompanied by run-down. The tetanic fade and the run-down became more pronounced for a time shortly after washout of toxins despite the restoration of single twitches and end-plate potential amplitudes, indicating the presynaptic origin of these effects induced by α-neurotoxins. We demonstrated that the functions of the pre- and postsynaptic acetylcholine receptors can be dissociated by using the different kinetics of toxin-receptor interactions. The results also implicate that a positive feedback enhancement of transmitter release operates via the presynaptic acetylcholine receptor in the neuromuscular junction in normal physiological conditions during repetitive pulses.