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 twitc h tension and electrophysical recording techniques using isolated skel etal muscle preparations. On chick biventer cervicis preparations, BT (1-3 mug/ml) augmented the twitch responses to indirect, but not direc t, muscle stimulation. Higher concentrations caused a transient augmen tation followed by a large contracture and then a reduction in twitch height. BT at the concentrations tested caused little change in postju nctional sensitivity as assessed by responses to exogenous acetylcholi ne, carbachol and KCl. Tubocurarine abolished the prolonged contractur e induced by BT (10 mug/ml) in the presence or absence of nerve stimul ation. On mouse hemidiaphragm preparations, BT (3-10 mug/ml) increased the twitch responses to indirect stimulation but caused little change in directly stimulated preparations. On mouse triangularis sterni pre parations, BT (3-10 mug/ml) increased quantal content of the evoked en d-plate potentials (epps) by about 70%, without markedly affecting the time course and amplitude of miniature epps. BT also caused repetitiv e epps in response to single shock nerve stimulation. Extracellular re cording of nerve terminal current waveforms in triangularis sterni pre parations revealed that BT (10-30 mug/ml) slightly reduced the amplitu de of the waveform. Subsequently, BT induced repetitive firing of nerv e endings in response to single shock stimulation, and eventually mark edly prolonged the time course of the nerve terminal waveform. The eff ects caused by BT were different from those caused by iberiotoxin, the blocker of Ca2+-activated K+ currents, isolated from BT. The effects were similar to those caused by ATX-II, a toxin that delays inactivati on of Na+ channels. However, BT and ATX-II behaved differently in the presence of K+ channel blockers, 3,4-diaminopyridine (DAP) and tetraet hylammonium (TEA). These results confirm that Buthus tamulus venom act s mainly prejunctionally to increase the release of acetylcholine. The effect of BT on the perineural waveforms suggests that some of its ac tions may be due to effects on Na+ channels at or near the nerve termi nals; however, additional effects on K+ channels are likely.