Botulinum toxin and 4-aminoquinoline induce a similar abnormal type of spontaneous quantal transmitter release at the rat neuromuscular junction

doi:10.1016/0006-8993(83)91123-X

Brain Research

Volume 264, Issue 1, 28 March 1983, Pages 89-97

https://doi.org/10.1016/0006-8993(83)91123-X Get rights and content

Abstract

Intracellular recordings from botulinum toxin type A (Bo Tx)-poisoned extensor digitorum longus muscles from adult rats have shown that the toxin initially reduced the frequency of miniature endplate potentials (m.e.p.ps) to about 1/200 of normal. After a few days the m.e.p.p. frequency rose and was subsequently maintained at a level of about 1/3 of that at normal endplates. Depolarization of the nerve terminals with 20–30 mK KCl-Ringer initially failed to affect the frequency of m.e.p.ps and later caused only a 2–3-fold increase in their frequency. The temperature dependence of m.e.p.p. frequency at BoTx-poisoned endplates had a Q₁₀ of about 12 compared to 2–3 for normal junctions. The time to peak of a population of m.e.p.ps at BoTx-poisoned junctions was prolonged as compared to normal and fast- and slow-rising m.e.p.ps originated within the same post-synaptic membrane field area.

M.e.p.ps in BoTx-poisoned muscles resembled the m.e.p.ps which 4-aminoquinoline (4-AQ) has been shown to induce in normal muscle, and we therefore examined and compared these two release processes for acetylcholine. Procedures known to markedly affect m.e.p.p. frequency at normal junctions, such as nerve terminal depolarization or changes in extra- and intracellular Ca²⁺ concentrations, failed to affect m.e.p.p. frequency in BoTx-poisoned muscles similarly the frequency of m.e.p.ps induced by 4-AQ in normal muscle. Tonicity changes in the extracellular medium altered m.e.p.p. frequency in both the experimental conditions, but in a direction opposite to that at normal junctions. The temperature dependence of the frequency of 4-AQ-induced m.e.p.ps was similar to that of m.e.p.ps at BoTx-poisoned junctions.

It is concluded that BoTx poisoning induces an abnormal type of spontaneous quantal transmitter release, characterized by being insensitive to nerve terminal depolarization and to transmembrane Ca²⁺ fluxes. This transmitter release has characteristics similar to that previously described for the release induced, at normal junctions, by 4-AQ.

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^*: Institut de Pharmacologie, Laboratoire Associe no 206, C.N.R.S., 15 Rue de l'Ecole de Médecine, 75270 Paris, France.

^**: Dept. of Neurology, University of Lund, Lund, Sweden.

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Botulinum toxin and 4-aminoquinoline induce a similar abnormal type of spontaneous quantal transmitter release at the rat neuromuscular junction

Abstract

J. neurosci. Sci.

Neuroscience

Abnormal myelination in transplanted Trembler mouse Schwann cells

Nature (Lond.)

Properties of spontaneous potentials at denervated motor endplates of the frog

Observations on the action of type A botulinum toxin on frog neuromuscular junctions

J. Physiol. (Lond.)

Discrepancies between spontaneous and evoked synaptic potentials at normal,regenerating and botulinum toxin poisoned mammalian neuromuscular junctions

Effects of botulinum toxin on neuromuscular transmission in the rat

J. Physiol. (Lond.)

Transmitter release properties along regenerated nerve processes at the frog neuromuscular junction

J. Neurosci.

Histological differences between soleus and gastrocnemius muscles in the mouse after the local injection of botulinum toxin

J. Physiol. (Lond.)