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Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin

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Summary

  1. 1.

    The blocking effect of tetanus toxin on the neuromuscular junction of the mouse phrenic nervehemidiaphragm preparation exposed to the toxin (0.05–20 μg/ml) in the organ bath was studied and compared with the action of botulinum A toxin.

  2. 2.

    The time course of the paralysis of the diaphragm could be divided into a latent and a manifest period. Still during the latent period the effect of the toxin became progressively resistant to washing and, with some delay, to antitoxin.

  3. 3.

    Between 25 and 41°C the time until paralysis strongly depended on temperature with Q 10 of about 2.7.

  4. 4.

    Procedures increasing the transmitter release shortened, and procedures depressing it prolonged the time until paralysis.

  5. 5.

    4-Aminopyridine and guanidine temporarily restored the contraction of the partially paralyzed diaphragm, indicating the persistence of activatable calcium and acetylcholine pools. Raising the external Ca2+-concentration and application of the Ca-Ionophore A 23187 were ineffective in the doses applied.

  6. 6.

    About 80 min after exposure to the toxin (10 μg/ml), the m.e.p.p. activity decreased by a factor of 30. Parallel to this, paralysis of nerve evoked muscle contraction developed.

  7. 7.

    Neuraminidase treatment did not prevent tetanus toxin poisoning.

  8. 8.

    The paralysis is produced by tetanus toxin itself and not by contaminants as shown by the parallel decrease of toxicity and paralysis following treatment with either antitoxin or brain homogenate, or by the use of spontaneously inactivated toxin.

  9. 9.

    Tetanus toxin was compared with botulinum A toxin as to the shape of its dose-response curve, time course of paralysis, temporary reversal by 4-aminopyridine and behaviour against Ca-ionophore. In any case, both toxins were indistinguishable, albeit botulinum A neurotoxin was calculated to be about 2000 times more potent than tetanus toxin.

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Authors and Affiliations

  1. Rudolf-Buchheim-Institut für Pharmakologie der Justus Liebig-Universität Giessen, Frankfurter Strasse 107, D-6300, Giessen, Germany

    E. Habermann, F. Dreyer & H. Bigalke

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  1. E. Habermann
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  2. F. Dreyer
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  3. H. Bigalke
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Habermann, E., Dreyer, F. & Bigalke, H. Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin. Naunyn-Schmiedeberg's Arch. Pharmacol. 311, 33–40 (1980). https://doi.org/10.1007/BF00500299

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  • DOI: https://doi.org/10.1007/BF00500299

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