Correlation between Ultrastructural and Molecular Changes in Denervated Muscle: a Paradigm Based on Functional Electrical Stimulation

Soon after denervation, skeletal muscle undergoes ultrastructural and molecular changes that ultimately lead to muscle atrophy and cell death. Functional electrical stimulation (FES) is effective in preventing the atrophy of denervated muscles, but it is unclear whether FES can prevent the progression of ultrastructural changes in the sarcotubular system and cell death after denervation. In this work, we developed a model to study the effects of FES on the ultrastructural changes in the sarcotubular system and the cell death which follow skeletal muscle denervation. The right sciatic nerve of adult rats was sectioned and after 1 day, and 1, 2 and 3 weeks the tibialis anterioris muscle was electrically stimulated. FES was done for 1, 2, 3, 10 and 20 weeks after denervation. The stimuli (10 Hz) were given for 10 s followed by a 10 s rest for a total of 30 min/day. Transmission electron microscopy showed that progressive dilatation of the sarcotubular system, as well as signs of cell death, were prevented when stimulation was started one day or one week after denervation. This model could be useful for understanding the correlation between the structural changes and the molecules involved in the dilatation of the sarcotubular system or cell death.