Multidirectional effect of low-intensity neuromuscular electrical stimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse

Low-intensity neuromuscular electrical stimulation (NMES) is often used as an alternative to exercise and high-intensity electrical stimulation to prevent the loss of muscle mass, strength, and endurance in spaceflight and in patients with severe chronic diseases. This study investigated the effects of a one-week disuse, both with and without low-intensity neuromuscular electrical stimulation – a safe (non-traumatic) approach to prevent the loss of muscle mass, on the functional capacities and gene expression in thigh and calf muscles. This study assessed the efficiency of low-intensity (~10% of maximal voluntary contraction) electrical stimulation in preventing the negative effects of 7-day disuse (dry immersion without [see a related dataset GSE271607] and with daily stimulation) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle. Application of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of the knee extensors, as well as a decrease in maximal (intrinsic) ADP-stimulated mitochondrial respiration and changes in the expression of genes encoding mitochondrial, extracellular matrix, and membrane proteins in the vastus lateralis muscle. In contrast, for the ankle plantar flexors/soleus muscle, electrical stimulation had a positive effect only on maximal mitochondrial respiration, but slightly accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be related to the activation of inflammatory genes. The data obtained open up broad prospects for the use of low-intensity electrical stimulation to prevent the negative effects of disuse for “mixed” muscles, meanwhile, the optimization of the stimulation protocol is required for “slow” muscles.