Low-frequency stimulation regulates metabolic gene expression in paralyzed muscle

The altered metabolic state after a spinal cord injury compromises systemic glucose regulation. Skeletal muscle atrophies and transforms into fast, glycolytic, and insulin-resistant tissue. Osteoporosis is common after spinal cord injury and limits the ability to exercise paralyzed muscle. We used a novel approach to study the acute effect of two frequencies of stimulation (20 and 5 Hz) on muscle fatigue and gene regulation in people with chronic paralysis. Twelve subjects with chronic (>1 yr) and motor complete spinal cord injury (ASIA A) participated in the study. We assessed the twitch force before and after a single session of electrical stimulation (5 or 20 Hz). We controlled the total number of pulses delivered for each protocol (10,000 pulses). Three hours after the completion of the electrical stimulation (5 or 20 Hz), we sampled the vastus lateralis muscle and examined genes involved with metabolic transcription, glycolysis, oxidative phosphorylation, and mitochondria remodeling. We discovered that the 5-Hz stimulation session induced a similar amount of fatigue and a five- to sixfold increase (P < 0.05) in key metabolic transcription factors, including PGC-1α, NR4A3, and ABRA as the 20-Hz session. Neither session showed a robust regulation of genes for glycolysis, oxidative phosphorylation, or mitochondria remodeling. We conclude that a low-force and low-frequency stimulation session is effective at inducing fatigue and regulating key metabolic transcription factors in human paralyzed muscle. This strategy may be an acceptable intervention to improve systemic metabolism in people with chronic paralysis.