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At least three sequential steps are involved in the tetanus toxin-induced block of neuromuscular transmission.

Tetanus toxin causes a block of the neuromuscular transmission. The kinetic aspects of the block were studied in vitro on the mouse phrenic nerve-hemidiaphragm exposed to toxin (1 microgram/ml). 1. The toxin action on the nerve ending involves three sequential steps: binding, "translocation" and paralysis. 2. Diffusion and binding of tetanus toxin molecules to the presynaptic membrane is complete in about 60 min. The binding step is irreversible, independent of transmitter release and of the temperature. Tetanus antitoxin, however, inactivates the bound toxin molecules. 3. After a second step which is probably due to a "translocation" of the toxin molecules into or through the presynaptic membrane the antitoxin molecules are now ineffective to prevent the toxin-induced inhibition of transmitter release. This so called "translocation" step requires transmitter release and therefore depends strongly on the frequency of nerve stimulation. 4. The paralytic step does not depend on the transmitter release. It, however, depends strongly on temperature with a break in the Arrhenius-plot around 33 degrees C which suggests the involvement of a phase transition rather than of an enzymatic activity of the toxin.

Animals↗

ATROPHY OF SKELETAL MUSCLE IN CHICK EMBRYOS TREATED WITH BOTULINUM TOXIN.

Botulinum toxin was given in large intravenous doses to 7- and 12- day chick embryos. Atrophy of skeletal muscle resulted without significant atrophy of other organs. The histological appearance of muscle was consistent with denervation. The results suggest that neural acetylcholine release may play a significant role in "trophic transmission" from nerve to muscle.

Abnormalities, Drug-Induced↗

Anthrax toxin: causative agent in the death of rhesus monkeys.

Anthrax toxin was present in the blood obtained from rhesus monkeys at the terminal stage of anthrax and was also present in increasing amounts in the lymph as death approached. When sterile toxin produced in vitro was injected in sufficient amounts, monkeys died unless they were injected with specific antiserum. Death with symptoms of toxemia occurred within 2 hours after injection of 10(11) spores, whereas 10(10) spores or less required 20 or more hours of growth in vivo to cause death.

Animals↗