Changes in motor innervation and cholinesterase localization induced by botulinum toxin in skeletal muscle of the mouse: differences between fast and slow muscles.

Botulinum toxin causes paralysis of skeletal muscle by preventing the release of acetylcholine at motor nerve terminals (Burgen, Dickens, and Zatman, 1949). It is known that, when a sub-lethal quantity of toxin is injected directly into muscles of experimental animals, paralysis and atrophy of those muscles develop and persist for a long time (Guyton and MacDonald, 1947; Jirmanova, Sobotkova, Thesleff, and Zelena, 1964; Duchen and Strich, 1967, 1968). A remarkable overgrowth of motor nerve fibres occurs while the muscles are paralysed and atrophied (Duchen and Strich 1968) and changes in the localization of cholinesterase activity develop. After some weeks muscular function recovers, the nerve growth ceases and then regresses, and the motor innervation of the muscle and the distribution of cholinesterase become reorganized. The pattern of innervation and the morphology of subneural apparatuses remain abnormal permanently. Although the histological investigations of Duchen and Strich (1968) showed that abnormalities develop in the innervation and in the morphology of the subneuralapparatuses, the exact relationship between the changes in cholinesterase localization and the sprouting of motor nerve fibres was not determined. This paper presents the result of recent histological studies of the effects of botulinum toxin on skeletal muscle of the mouse in which the relationship of the motor nerve growth to the development of abnormalities in cholinesterase and its localization was examined. In recent experiments it has become apparent that there are marked differences in the rate at which abnormalities develop in soleus and gastrocnemius and these differences can be correlated closely with the histological characteristics of these muscles which allow their muscle fibres to be designated as 'fast' or 'slow'. The differences in the histological changes induced by botulinum toxin in the various muscles are described in this paper. These observations have been briefly presented in a preliminary communication (Duchen, 1969).