Effects of crotoxin on the action potential kinetics of frog skeletal muscle

1. The effect of crotoxin on the action potential kinetics of frog (Rana catesbeiana; 60-80 g) skeletal muscle was studied using a modified Ringer solution containing 1.6 mM KCl. 2. Crotoxin affected the kinetics of the action potential in a dose-dependent manner (90 to 460 nM). At 230 nM, crotoxin prolonged the duration of the action potential (from 1.1 +/- 0.1 to 1.6 +/- 0.1 ms) and slowed the rates of depolarization (from 282.0 +/- 7.3 to 196.0 +/- 13.2 V/s) and repolarization (from -81.4 +/- 6.9 to -55.6 +/- 3.8 V/s), in a dose-dependent manner. Its phospholipase subunit (component B) was five times less effective. 3. No effect of crotoxin was observed in the presence of 2.5 mM KCl or when SrCl2 was substituted for CaCl2. Lowering the muscle temperature to 12 degrees C did not reduce the effect of crotoxin. 4. No effect on the passive membrane response to hyperpolarizing current pulses was observed, which implies no major effect on the membrane resistance and capacitance. 5. It is concluded that crotoxin reduces the Na+ current and slows down the repolarization mechanism. This effect is probably not dependent on the phospholipase A2 activity of crotoxin and is inhibited by the substitution of Sr2+ for Ca2+

The effect of crotoxin on the release of acetylcholine and lactate dehydrogenase from rat brain cortical slices

We have studied the effects of crotoxin, the neurotoxin of the South American rattlesnake Crotalus durissus terrificus, ,on the release of acetylcholine and lactate dehydrogenase from rat brain cortical slices. Crotoxin enhances the release of [3H]-acetylcholine from cortical slices (control values 92.8 ñ 5.9 and 150.3 ñ 11.7 DPM/mg and crotoxin valuesw 199.1 ñ 7.0 and 336.0 ñ 26.0 DPM/mg at 60 and 120 min incubation, respectively) in parallel with the release of lactate dehydrogenase (control values 50.4 ñ 16.8 and 80.3 ñ 19.5 U/mg and crotoxin values 162.5 ñ 39.1 and 355.7 ñ 38.2 U/mg, at 120 min incubation, respectively). Both effects are markedly reduced when substituting Sr2+ for Ca2+ in the incubation medium. It is concluded that the phospholipase activity of crotoxin is responsible for the observed effects