Pre‐ and post‐synaptic actions of botulinum toxin at the rat neuromuscular junction.

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Abstract
Extensor digitorum longus muscles of rats were paralyzed with local, non-lethal doses of botulinum toxin Type A (BoTx). At 2 and 7 days after toxin injection, the nerve-muscle preparations were excised and end-plate currents analyzed at 23.degree. C by dual-microelectrode voltage clamp. At 2 days after BoTx injection, the growth time of miniature end-plate currents MEPC increased from a rather narrow range with a mean of 0.59 to a mean of 1.35 ms with a large variability between MEPC. End-plate currents (EPC) were reduced compared to unpoisoned muscle. The decay phase of MEPC and EPC the growth phase of EPC and the voltage sensitivity of MEPC were unchanged. At 7 days after BoTx injection, the findings were similar to 2 days except that the time constant of the decay phase of MEPC and EPC was about twice as long as normal and that the voltage sensitivity of MEPC was increased. The acetylcholine null potential (.apprx. 0 mV) was unchanged after treatment with BoTx. The increase in the growth time of MEPC compared to EPS following the injection of BoTx suggests that the poisoning, besides blocking quantal release, affects the time course of spontaneous but not that of evoked release. After BoTx poisoning the trans-synaptic diffusion of a majority of spontaneously released transmitter quanta seems to occur more slowly or from areas more distant from the highest concentration of the post-synaptic receptor than that of evoked release. The increase in the decay phase of MEPC and EPC and its increased voltage sensitivity observed in muscles poisoned for 7 days with BoTx suggest the appearance at the end-plate of a population of new receptors with a prolonged ion channel opening time similar to that previously described for extrajunctional receptors after denervation and for junctional receptors during development.