Botulinum neurotoxin type A causes shifts in myosin heavy chain composition in muscle

Botulinum neurotoxin type A has gained widespread use for treatment of a host of neuromuscular conditions. However, the potential effect of this toxin has on the histological and biochemical properties of skeletal muscle remains largely unexplored. The purpose of this study was to characterize the myosin heavy chain (MHC) distribution of adult rat skeletal muscle treated with botulinum neurotoxin type. Varying doses of the toxin were injected into the triceps surae muscle group of one hind limb. Force production was assessed periodically to access the functional deficit incurred. After 10 weeks, animals were sacrificed, muscles removed, and MHC composition determined. Body weight, muscle weight and force of the injected leg were significantly reduced in all groups, while loss of muscle weight and force in the contralateral leg was variable. In the injected plantaris and gastrocnemius muscles, type I MHC increased approximately 100%, while type IIa/x decreased approximately 50%. In the contralateral gastrocnemius, types I and IIa/x MHC increased approximately 100%, while type IIb decreased approximately 45%. These data suggest that botulinum neurotoxin causes shifts in MHC composition in injected and contralateral muscles that are contrary to those seen with denervation and similar to those seen with aging.