Enhancement by Anemonia sulcata toxin II of spontaneous quantal transmitter release from mammalian motor nerve terminals.

The action of Anemonia sulcata toxin II (ATX-II) on spontaneous quantal transmitter release from motor nerve terminals was investigated by recording miniature end-plate potentials (MEPPs) from isolated mouse phrenic nerve--hemidiaphragm nerve--muscle preparations. ATX-II (3.2 microM) when applied for 3-40 min to junctions bathed in a normal ionic medium enhanced about one hundred fold the rate of spontaneous MEPPs. Concomitantly, ATX-II depolarized the muscle fiber. The effect of the toxin on MEPP frequency was markedly reduced when junctions were exposed to Na-deficient solutions or pre-treated with dantrolene sodium (10 microM). ATX-II (0.24-3.2 microM) increased MEPP rate in junctions exposed to a Ca-free medium containing 2 mM EGTA and 2 mM Mg2+ in a dose- and time-dependent manner. Tetrodotoxin (0.2-1 microM) prevented the effects of ATX-II on MEPP frequency and on the resting membrane potential of muscle fibers. Tetrodotoxin also antagonized the acceleration of MEPP induced by ATX-II. The experimental findings suggest that ATX-II acts to increase quantal transmitter output from motor nerve terminals by enhancing Na+ influx through tetrodotoxin-sensitive presynaptic channels, since ATX-II action does not appear to depend upon entry of Ca2+ from the extracellular medium. It is likely that ATX-II, by increasing intraterminal Na+ concentration, may trigger calcium release from internal stores.

[Effects of a neurotoxin isolated from the sea anemone, Anemonia sulcata, at frog neuromuscular junction (author's transl)]. / Action d'une neurotoxine isolée de l'anémone de mer (Anemonia sulcata) à la jonction neuromusculaire de grenouille.

ATX II is a toxin extracted from tentacles of Anemonia sulcata. It was known that this protein displays neurotoxic effects on frog isolated neuromuscular preparation (Fig. 1, 2) and that muscular contractures observed with ATX II are blocked by d-tubocurarine (Fig. 3) or on a 40-days-denervated gastrocnemius (Fig. 4). Part of these experiments has already appeared. 1. These effects of ATX II depend on calcium concentration in the bathing medium, as is the case for transmitter release. The same results were observed when we substituted strontium to calcium. 2. On an intact sciatic sartorius preparation, ATX II does not act on the amplitude of the miniature endplate potentials (mepps, Fig. 6). The muscular action potential is not modified by this toxin. 3. ATX II increases the frequency of the mepps (Fig. 5). The evoked transmitter release (quantal content) after ATX II is also largely increased (Fig. 7). 4. In conclusion, it is suggested that ATX II acts indirectly on the muscle through an increase in acetylcholine release from the motor nerve terminals.

[Comparative action of toxins isolated from the venom of the scorpion (Androctonus australis) and the tentacles of the sea anemone (Anemonia Sulcata) on an isolated frog neuromuscular preparation]. / Action comparative des toxines isolées du venin Scorpion (Androctonus australis) et des tentacules d'Anémone de mer (Anemonia Sulcata) sur une préparation neuro-musculaire isolée de Grenouille.

We have shown that, if Scorpion venom is acting a skeletal muscle indirectly by releasing Acetycholine and directly by inducing an increase in intracellular free calcium, the main action of toxin II isolated from Anemonia Sulcata tentacles is presynaptic.

[Action of serotonin on neuromuscular transmission in normal guinea pigs and those treated with paralyzing doses of botulinum toxin type A]. / Action de la sérotonine sur la transmission neuro-musculaire de cobaye normal et traité par des doses paralysantes de toxine botulique type A.

Serotonin inhibits the muscular contractions elicited by indirect stimulation; injected before Botulinum toxin it prevents the paralysis induced by this toxin.

[Action of toxin II isolated from the tentacles of sea anemones on the neuromuscular transmission on normal and botulin toxin inhibited frogs]. / Action de la toxine IL isolée des tentacules d'Anémone de mer sur la transmission neuro-musculaire de Grenouille normale et inhibée par la toxine botulique.

In our experimental conditions, toxin II from Anemonia sulcata restored Frog neuromuscular transmission blocked by botulinum toxin, type A.

[Effect of scorpion venom (Androctonus australis) on neuromuscular transmission inhibited by botulinum toxin in the frog]. / Action du venin de scorpion (Androctonus australis) sur la transmission neuro-musculaire de grenouille inhibée par la toxine botulique.

We have shown that Scorpion venom restores the neuro-muscular transmission inhibited by Botulinum toxin in the Frog. The effectiveness of Scorpion venom was antagonized by excess magnesium.

[Action of toxins isolated from scorpion and sea anemone venoms on ileum isolated from reserpine-treated guinea pigs]. / Action des toxines isolées des venins de scorpion et d'anémone de mer sur l'iléon isolé de cobaye traité auparavant par la réserpine.

We have shown that the ileum isolated from a reserpinized guinea Pig does respond to toxin II obtained from Scorpion venom but does not react to Anemonia sulcata toxin. We conclude that if Acetylcholine is the neurotransmitter inducing pharmacological activity of Scorpion toxin it is serotonin which triggers activity of Anemonia sulcata toxin in ileum of a normal guinea Pig.

[The effect of toxin II isolated from sea anemones (Anemonia sulcata) on the isolated guinea pig ileum]. / Action de la toxine II isolée de l'anémone de mer (Anemonia sulcata) sur l'iléon isolé de cobaye.

When the guinea-pig isolated ileum is treated with the Toxin II from Anemonia sulcata, it releases not only acetylcholine but also serotonin. These transmitters are both involved in the spasmogenic action of the toxin.

[Pharmacologic properties of the toxins isolated from the sea anemone (Anemonia sulcata)]. / Propriétés pharmacologiques des toxines isolées de l'anémone de mer (Anemonia sulcata

We have shown that if toxin II isolated from Anemonia sulcata is mainly cardiotoxic on Rats it nevertheless displays neurotoxic effects. Furthermore it releases acetylcholine from isolated Guinea Pig ileum.

[Effect of sodium deprivation on the isolated guinea pig ileum in a physiological medium or in the presence of scorpion venom]. / Effets de la privation de sodium sur l'ilón isolé de cobaye dans un milieu physiologique normal et additionné de venin de scorpion

We concluded from our results that contractures which occurred when NaCl is replaced by other substitutes could be due to increased Ca entry. This ionic disturbance does not produce any increase of the resting acetylcholine output such as that described for the innervated longitudinal muscle obtained from the ileum. In this environment, venom from the Scorpion (Androctonus australis) is shown to have no effect.

[Lanthanum and scorpion venom on the isolated guinea pig ileum]. / Lanthane et venin de Scorpion sur l'iléon isolé de Cobaye

In the guinea-pig isolated ileum, lanthanum increases the quantity of spontaneously released acetylcholine and induces contracture of this muscle. We have shown that the latter phenomenon is not a consequence of the former. We conclude that it could be due to the Ca++ displaced by La+++. The scorpion venom effects are abolished by lanthanum. We explain this observation by blockage of Ca++ fluxes.

[The effect of scorpion venom (Androctonus australis) on a frog neuromuscular preparation]. / Action du venin de scorpion (Androctonus australis) sur une préparation neuro-musculaire de grenouille

We have shown that d-tubocurarine inhibits the effects of scorpion venom in striated muscles of the frog; we concluded that this venom acts mainly by releasing acetylcholine from the nerve terminal. Furthermore, scorpion venom is able to displace intracellular calcium.

[Cardiotoxicity in rats of purified gamma toxin isolated from venom of Naja nigricollis and of toxins extracted from scorpion venom]. / Cardiotoxicité chez le rat de la toxine gamma purifiée, isolée du venin de Naja nigricollis et des toxines extraites du venin de scorpion

In vivo, atropine or tetrodotoxin prevent arrhytmias which are due to acetylcholine released by the scorpion's venom. On the contrary, atropine is ineffective against cardiotoxicity of the purified gamma toxin and tetrodotoxin aggravates its effects. These findings allow us to postulate the mechanism of action which differs in these two toxin groups.