Effects of scorpion (Buthus tamulus) venom on neuromuscular transmission in vitro

The effects of venom from the Indian red scorpion Buthus tamulus (BT) on neuromuscular transmission have been investigated by means of twitch tension and electrophysical recording techniques using isolated skeletal muscle preparations. On chick biventer cervicis preparations, BT (1-3 micrograms/ml) augmented the twitch responses to indirect, but not direct, muscle stimulation. Higher concentrations caused a transient augmentation followed by a large contracture and then a reduction in twitch height. BT at the concentrations tested caused little change in postjunctional sensitivity as assessed by responses to exogenous acetylcholine, carbachol and KCl. Tubocurarine abolished the prolonged contracture induced by BT (10 micrograms/ml) in the presence or absence of nerve stimulation. On mouse hemidiaphragm preparations, BT (3-10 micrograms/ml) increased the twitch responses to indirect stimulation but caused little change in directly stimulated preparations. On mouse triangularis sterni preparations, BT (3-10 micrograms/ml) increased quantal content of the evoked end-plate potentials (epps) by about 70%, without markedly affecting the time course and amplitude of miniature epps. BT also caused repetitive epps in response to single shock nerve stimulation. Extracellular recording of nerve terminal current waveforms in triangularis sterni preparations revealed that BT (10-30 micrograms/ml) slightly reduced the amplitude of the waveform. Subsequently, BT induced repetitive firing of nerve endings in response to single shock stimulation, and eventually markedly prolonged the time course of the nerve terminal waveform. The effects caused by BT were different from those caused by iberiotoxin, the blocker of Ca(2+)-activated K+ currents, isolated from BT. The effects were similar to those caused by ATX-II, a toxin that delays inactivation of Na+ channels. However, BT and ATX-II behaved differently in the presence of K+ channel blockers, 3,4-diaminopyridine (DAP) and tetraethylammonium (TEA). These results confirm that Buthus tamulus venom acts mainly prejunctionally to increase the release of acetylcholine. The effect of BT on the perineural waveforms suggests that some of its actions may be due to effects on Na+ channels at or near the nerve terminals; however, additional effects of K+ channels are likely.