Low‐frequency electrical stimulation prevents muscle loss in mice with chronic kidney disease (CKD) by decreasing atrogin1 and MurF‐1 expression

Hypothesis Low‐frequency electrical stimulation (LFES) in muscle attenuates muscle atrophy induced by CKD. Method CKD was induced in 20g mice by 5/6th nephrectomy. Electrode insertion points were selected using acupunture therapy guidelines. The positive needle was inserted under the fibula head near the superficial and deep fibular nerves (site name: Yang ling qian). The negative needle was inserted lateral to the knee joint under the fibula head near the fibular nerve (site name: Ho san li). The needles were connected to an SDZ‐蕅 electronic acupuncture device delivering a constant electical pulse (20Hz, 1mA) daily for 15 minutes over 4 weeks. Results Soleus and EDL muscle weights from uremic mice were significantly increased by LFES (P<0.05). LFES blunted the increase in CKD‐induced muscle proteolysis and improved phosphorylation of Akt (2.3‐fold, P<0.001) and FoxO3a (2.1‐fold, P<0.01). mRNAs of proteolytic atrogin‐1 and MuRF‐1 E3 ubiquitin ligases were attenuated by LFES. LFES concomitantly improved protein synthesis (increased phosphorylation of mTOR and p70S6K) and myogenesis (increased levels of MyoD, myogenin, and eMyHC) in muscles of CKD mice. Conclusions LEFS can prevent CKD‐induced muscle loss by a multi‐faceted mechanism affecting myogenesis, protein degradation and synthesis. Support: NIH AR060268 , and the NSF of China (30971471)