Effects of botulinum toxin on the distribution of succinate dehydrogenase and phosphorylase in fast and slow skeletal muscles of the mouse

Abstract

SUMMARY A sublethal quantity of botulinum toxin was injected into the muscles of one leg in mice. The histochemical localization of succinate dehydrogenase (SD) and phosphorylase (P) in soleus and gastrocnemius was studied at intervals of from one week to 15 months after the injection of toxin. In normal mice the fibres of soleus are rich in SD and poor in P, but in the superficial part of gastrocnemius the majority of fibres are rich in P and poor in SD. After the injection of toxin the muscles became paralysed and atrophied for several weeks during which time the fibres of gastrocnemius lost their staining reactivity for P and the fibres of soleus showed a weakening of the SD reaction. With the recovery from the effects of the toxin the muscle fibres increased in size and in P activity. Recovery commenced sooner in soleus than in gastrocnemius and for several weeks soleus fibres showed a stronger reaction for P than normal, but with longer survival the enzyme reactions in soleus became normal. Recovery in gastrocnemius began about six weeks after the injection of toxin. Many muscle fibres in gastrocnemius became much enlarged while others remained atrophied. Many fibres gave a strong histochemical reaction for both enzymes. These abnormalities in gastrocnemius seemed to be permanent.Skeletal muscles are composed of different types of muscle fibre which have distinctive morphological and physiological characteristics. In experiments in which the local effects of botulinum toxin were studied it was shown that the changes induced by the toxin in skeletal muscles of the mouse varied very strikingly from one muscle to another. Botulinum toxin causes temporary paralysis of muscle by blocking neuromuscular transmission and this block is overcome by the sprouting of motor nerves and the formation of new end-plates (Duchen and Strich, 1968). The rate of recovery from the effects of the toxin is more rapid in soleus than in gastrocnemius (Duchen, 1970a) in which histological abnormalities persist for many months. In the mouse, as in most mammals, soleus is a 'slow', red muscle while the superficial part of gastrocnemius consists of 'fast', white muscle. In recent years, the histochemical demonstration of various enzymes of skeletal muscle fibres has shown that the slow red muscles are composed of fibres rich in oxidative mitochondrial enzymes while the fast white muscle fibres are rich in phosphorylase (see Dubowitz, 1968). This paper reports the results of histochemical studies of the changes in slow and fast muscles after the local injection of botulinum toxin. The distribution of succinate dehydrogenase, representing the mitochondrial enzymes, and of phosphorylase was followed in soleus and gastrocnemius of the mouse for up to 15 months after the injection of toxin. This period of time includes an initial phase of paralysis and atrophy of muscle fibres followed by progressive recovery from the effects of the toxin. MATERIAL AND METHODSA sublethal quantity of type A botulinum toxin was injected into the calf muscles o...