Abstract
Spinal cord injury (SCI) is associated with muscle atrophy, transformation of muscle fibers to a fast fatigable phenotype, metabolic inflexibility (diabetes), and neurogenic osteoporosis. Electrical stimulation of paralyzed muscle may mitigate muscle metabolic abnormalities after SCI, but there is a risk for a fracture to the osteoporotic skeletal system. The goal of this study was to determine if low force stimulation (3 Hz) causes fatigue of chronically paralyzed muscle consistent with selected muscle gene expression profiles. We tested 29 subjects, nine with a SCI and 20 without and SCI, during low force fatigue protocol. Three SCI and three non-SCI subjects were muscle biopsied for gene and protein expression analysis. The fatigue index (FI) was 0.21 ± 0.27 and 0.91 ± 0.01 for the SCI and non-SCI groups, respectively, supporting that the low force protocol physiologically fatigued the chronically paralyzed muscle. The post fatigue potentiation index (PI) for the SCI group was increased to 1.60 ± 0.06 (P <0.001), while the non-SCI group was 1.26 ± 0.02 supporting that calcium handling was compromised with the low force stimulation. The mRNA expression from genes that regulate atrophy and fast properties (MSTN, ANKRD1, MYH8, and MYCBP2) was up regulated, while genes that regulate oxidative and slow muscle properties (MYL3, SDHB, PDK2, and RyR1) were repressed in the chronic SCI muscle. MSTN, ANKRD1, MYH8, MYCBP2 gene expression was also repressed 3 h after the low force stimulation protocol. Taken together, these findings support that a low force single twitch activation protocol induces paralyzed muscle fatigue and subsequent gene regulation. These findings suggest that training with a low force protocol may elicit skeletal muscle adaptations in people with SCI.