CONVULXIN, A NEW TOXIN FROM THE VENOM OF THE SOUTH-AMERICAN RATTLESNAKE CROTALUS-DURISSUS-TERRIFICUS

196875

UNEQUAL DEPOLARIZATION OF THE MEMBRANE OF THE RAT DIAPHRAGM MUSCLE-FIBERS CAUSED BY VERATRINE

4041454

EFFECTS AND MECHANISM OF ACTION OF TITYUS-SERRULATUS VENOM ON SKELETAL-MUSCLE

5213715

Nature of the postsynaptic action of crotoxin at guinea-pig diaphragm end-plates

Crotoxin is known to desensitize the nicotinic receptor of Torpedo marmorata and Electrophorus electricus electroplaques. The aim of the present study was to elucidate whether the postsynaptic effect of crotoxin at a mammalian muscle end-plate is also caused by receptor desensitization or results from a curaremimetic action. For this purpose, we investigated the action of 4-aminopyridine (4-AP) on crotoxin-induced blockade of miniature end-plate potentials (m.e.p.p.s) and of the depolarization of end-plates produced by carbachol. The experiments were carried out in guinea-pig diaphragms bathed in Tyrode solution at 37 degrees C and gassed with 95% O-2, 5% CO2. The potentials were measured with conventional techniques using glass microelectrodes. Even at low concentrations, crotoxin blocked the m.e.p.p.s and this blockade was antagonized by 4-AP. Neostigmine was without effect. 4-AP did not restore the m.e.p.p.s blocked by either d-tubocurarine (dTc) or beta-bungarotoxin (beta-BTX). 4-AP also antagonized the crotoxin-induced blockade of the end-plate depolarization produced by carbachol. These results show that the postsynaptic effect of crotoxin at the guinea-pig muscle end-plate also results from nicotinic receptor desensitization.91334

MODE OF ACTION OF THE CORAL SNAKE MICRURUS-SPIXII VENOM AT THE NEUROMUSCULAR-JUNCTION

The venom of Micrurus spixii, a coral snake dispersed throughout the Amazon Valley induces neuromuscular blockade in the rat phrenic nerve-diaphragm preparation and in the chick biventer cervicis nerve-muscle preparation. In both tissues, the venom does not depress the twitch response elicited by direct muscle stimulation. The depolarization produced by carbachol in the rat diaphragm and the contractures induced by acetylcholine (ACh) in the denervated rat hemidiaphragm and in the chick biventer cervicis muscle are inhibited by low venom concentrations. The frequency and, in several experiments, the amplitude of the miniature end-plate potentials (m.e.p.p.s) are increased by the venom. The m.e.p.p. amplitude always decreases before their disappearance. 3,4-Diaminopyridine (3,4-DAP) antagonizes the effect of the venom on neuromuscular transmission in the rat phrenic nerve-diaphragm and on the depolarization produced by carbachol in this preparation. It also antagonizes the venom-induced blockade of the m.e.p.p.s and increases the end-plate potential (e.p.p.) after the blockade produced by the venom in the rat phrenic nerve-diaphragm. The 3,4-DAP antagonistic effect on the postsynaptic action of the venom suggests that desensitization of the end-plate receptors is induced by the venom and is the main cause of the neuromuscular blockade that it produces.41193

Actions of Androctonus australis and Leiurus quinquestriatus venoms in the rat isolated atria and anesthetized rats; effect of magnesium and lidocaine

In rat isolated atria, Androctonus australis (Aa), Leiurus quinquestriatus quinquestriatus (Lqq), and L.q. hebraceus (Lqh) venoms produced intense contracture, alterations in the force and frequency of the spontaneous atrial contractions, and delayed afterdepolarizations (DAD). It was shown by means of tetrodotoxin-induced blockade of neurotransmitter release that the contracture and DAD were produced by the action of the venoms on the atrial cell membrane (direct action) while alterations in the force and frequency of the spontaneous atrial contractions were caused by acetylcholine and norepinephrine released by the venoms (indirect action). The irregularities in the spontaneous contractions and DAD were suppressed by magnesium and lidocaine which, however, caused only a small reduction in the intensity of the atrial contracture. The venom-induced DAD was also abolished by ryanodine and intensified by an increase in [Ca2+](0). In anesthetized rats, Aa, Lqq, and Lqh venoms induced hypertension, arrhythmias, and T wave inversion. The arrhythmias included bradycardia, ventricular and supraventricular extrasystoles, unsustained and sustained ventricular tachycardia with torsade de pointes episodes. Magnesium and lidocaine abolished them, and magnesium also counteracted the hypertension. These results suggest that magnesium and lidocaine, particularly magnesium, may be useful in the treatment of the arrhythmias, hypertension, and other disorders associated with Buthinae scorpion envenomation.11111

The pharmacological effect of Bothrops neuwiedii pauloensis (jararaca-pintada) snake venom on avian neuromuscular transmission

The neuromuscular effects of Bothrops neuwiedii pauloensis (jararaca-pintada) venom were studied on isolated chick biventer cervicis nerve-muscle preparations. Venom concentrations of 5-50 µg/ml produced an initial inhibition and a secondary increase of indirectly evoked twitches followed by a progressive concentration-dependent and irreversible neuromuscular blockade. At venom concentrations of 1-20 µg/ml, the responses to 13.4 mM KCl were inhibited whereas those to 110 µM acetylcholine alone and cumulative concentrations of 1 µM to 10 mM were unaffected. At venom concentrations higher than 50 µg/ml, there was pronounced muscle contracture with inhibition of the responses to acetylcholine, KCl and direct stimulation. At 20-24ºC, the venom (50 µg/ml) produced only partial neuromuscular blockade (30.7 ± 8.0%, N = 3) after 120 min and the initial inhibition and the secondary increase of the twitch responses caused by the venom were prolonged and pronounced and the response to KCl was unchanged. These results indicate that B.n. pauloensis venom is neurotoxic, acting primarily at presynaptic sites, and that enzyme activity may be involved in this pharmacological action