Blockade of neuromuscular transmission by enzymatically active and inactive beta-bungarotoxin.

Abstract

.beta.-Bungarotoxins are presynaptic blockers of neuromuscular transmission. The most positively charged .beta.-bungarotoxin that elutes from a CM-Sephadex C-25 column was used. The toxin was a single polypeptide with a MW of approximately 11,000 and had phospholipase A2 activity. The application of the enzymatically active toxin to the frog sciatic nerve-sartorius muscle preparation resulted in an initial decrease in the average endplate potential amplitude followed by a temporary rebound in endplate potential amplitude, and finally a complete inhibition of endplate potentials. Similarly, miniature endplate potential frequency was initially reduced upon toxin application but then increased dramatically. After the phospholipase A2 of the toxin was inactivated, treatment with the toxin resulted in only the initial decrease in transmitter release. Apparently this .beta.-bungarotoxin acts in 2 functionally separate steps: by binding to a specific presynaptic site possibly associated with Ca2+ entry, and by perturbing the presynaptic membrane by its enzyme action, which results in an increase and then a failure in transmitter release.