Belt electrode-tetanus muscle stimulation prevents denervation-induced atrophy of rat multiple skeletal muscle groups via ribosome biogenesis

Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to simultaneously contract multiple muscle groups. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly via mitochondrial biosynthesis. In this study, we examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for 1 week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague Dawley rats using belt electrodes attached to both ankle joints. In acute stimulation, a significant decrease in glycogen content in the left and right TA and GAS was observed, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES also enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN+electrically stimulated with B-SES (DEN+ES) groups. After 7 days of treatment, muscle wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN+ES groups compared to those in the CON group. The DEN+ES group showed significantly higher muscle weight and CSA than the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial and ribosome biogenesis are key events in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 45S (n = 6) levels in the DEN+ES group were higher than those in the DEN group. The mRNA levels of the muscle proteolytic molecules Atrogin-1 and MuRF1 were significantly higher in DEN than in CONT but were suppressed in DEN+ES. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes was effective in preventing denervation-induced atrophy in multiple muscle groups. Unlike twitch contractions, ribosomal biosynthesis plays a key role in tetanic contractions to prevent muscle atrophy.