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

Purpose: 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. Methods: 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 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. Results: 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. Conclusion: 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. © 2025 Elsevier B.V., All rights reserved.