Effect of botulinum toxin on trophic regulation of acetycholine receptors

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 density^2-5. 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 role^6-11, it has also been suggested that unrelated factors (for example, substances carried by axonal transport) exert some trophic regulatory influence on extrajunctional ACh receptors^12-14. 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.