Effect of botulinum toxin on trophic regulation of acetylcholine receptors.

Abstract

THE distribution of acetylcholine [ACh] receptors in mammalian skeletal muscle is regulated to a large extent by motor nerves1. In innervated muscles, ACh receptors are localised almost exclusively at neuromuscular junctions, but after denervation there is a great increase of extrajunctional receptor density2–5. The trophic mechanisms by which motor nerves normally control extrajunctional ACh receptor density are not well understood. Although ACh transmission and the muscle usage it produces have been shown to play an important role6–11, it has also been suggested that unrelated factors (for example, substances carried by axonal transport) exert some trophic regulatory influence on extrajunctional ACh receptors12–14. Since more than one factor may participate in this regulation, it is important to evaluate the relative contributions of each in quantitative terms. We have therefore made a quantitative comparison of the effects of botulinum toxin and surgical denervation on ACh receptors. Botulinum toxin blocks quantal release of ACh at nerve terminals15 in a highly specific manner that is thought to involve the vesicle release mechanism16. An 125I-α-bungarotoxin binding technique was used for quantitative determination of ACh receptor density17. The results indicate that blockade of ACh transmission by botulinum toxin produces a partial denervation-like increase in extrajunctional ACh receptors, similar to, but somewhat greater than that seen after disuse alone17.