Abstract
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1.
The action of the crude venom of the scorpionButhus tamulus and of three highly purified neurotoxic fractions were studied in voltage-clamp experiments with single nerve fibres of the toadXenopus laevis.
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2.
Both crude venom and the fractions studied reduced the sodium current and slowed down the inactivation of the sodium permeability.
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3.
The toxin effects developed mainly in 2 or 3 min (15°C) and were almost irreversible after washing with Ringer solution.
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4.
With positive pulses an inward- or outward-directed plateau of the sodium current seemed to be reached after a few 100 ms. It was sensitive to TTX. During very long pulses (50 s) a further decay of the current was seen.
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5.
When a positive pulse to −26 mV inducing a maintained inward current was followed by a positive pulse to −1 mV the inward current increased to a new level.
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6.
At potentials >−30 mV the steady-state inactivation of the sodium system decreased again.
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7.
When scorpion toxin was applied in the presence of 100 nmol/l TTX no slowing down of the sodium current occurred, indicating a protecting effect of TTX.
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8.
50 to 100 mg/l crude venom reduced the peak sodium current by 50%.
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9.
In a dose-response relation the effect of the toxins was taken as the current after 30 ms related to the peak sodium current. Although fraction V had a molecular weight of only 4400 it exerted no peculiar effects as compared to fractions XII and XIII (MW 7500 and 8000). The half values of the maximal effects of the toxins were at concentrations around 1 μmol/l.
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10.
It is suggested (I) that a smaller part only of the molecule inherent in all fractions is responsible for the toxic effects and (II) thatButhus tamulus toxins bind to channel proteins in the vicinity of the TTX receptor at the external membrane surface and by an allosteric reaction of channel proteins impede or even immobilize the inactivation mechanism and render it leaky.
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Siemen, D., Vogel, W. Tetrodotoxin interferes with the reaction of scorpion toxin (Buthus tamulus) at the sodium channel of the excitable membrane. Pflugers Arch. 397, 306–311 (1983). https://doi.org/10.1007/BF00580266
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DOI: https://doi.org/10.1007/BF00580266