High frequency electrical stimulation of sciatic nerve enhances skeletal muscle autophagy in mice

The aim of the present study was to investigate the effects of exercise on skeletal muscle autophagy. Trains of high-frequency electrical stimulation (pulses frequency: 100 Hz) were used to stimulate sciatic nerve and consequently induce muscle contraction of the left hindlimb. The unstimulated right hindlimb muscles were taken as control. The mice were sacrificed immediately (0), 30 or 60 min after the electrical stimulation by cervical dislocation, and gastrocnemius muscles were rapidly dissected and freeze-clamped in liquid nitrogen. AMP-activated protein kinase (AMPK) and the autophagy marker protein LC3 were detected by Western blotting, and muscle atrophy related genes including atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL were detected by using real-time qPCR. The results showed that, at 0 min after the electrical stimulation, the activity of AMPK and LC3-II/I ratio were significantly increased in left gastrocnemius muscles, compared with those of the muscles in the right hindlimb. The levels of atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL mRNA expressions were up-regulated by electrical stimulation. Meanwhile, the activity of autophagy related protein, ULK1 was significantly enhanced by electrical stimulation. These results suggest that electrical stimulation of sciatic nerve may induce the skeletal muscle autophagy, and this may be regulated through AMPK/ULK1-mediated signaling pathway.