| First Author | Baltgalvis KA | Year | 2011 |
| Journal | Skelet Muscle | Volume | 1 |
| Issue | 1 | Pages | 32 |
| PubMed ID | 21995957 | Mgi Jnum | J:183731 |
| Mgi Id | MGI:5319148 | Doi | 10.1186/2044-5040-1-32 |
| Citation | Baltgalvis KA, et al. (2011) Transgenic overexpression of gamma-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice. Skelet Muscle 1(1):32 |
| abstractText | ABSTRACT: BACKGROUND: gamma-cytoplasmic (gamma-cyto) actin levels are elevated in dystrophin-deficient mdx mouse skeletal muscle. The purpose of this study was to determine whether further elevation of gamma-cyto actin levels improve or exacerbate the dystrophic phenotype of mdx mice. METHODS: We transgenically overexpressed gamma-cyto actin, specifically in skeletal muscle of mdx mice (mdx-TG), and compared skeletal muscle pathology and force-generating capacity between mdx and mdx-TG mice at different ages. We investigated the mechanism by which gamma-cyto actin provides protection from force loss by studying the role of calcium channels and stretch-activated channels in isolated skeletal muscles and muscle fibers. Analysis of variance or independent t-tests were used to detect statistical differences between groups. RESULTS: Levels of gamma-cyto actin in mdx-TG skeletal muscle were elevated 200-fold compared to mdx skeletal muscle and incorporated into thin filaments. Overexpression of gamma-cyto actin had little effect on most parameters of mdx muscle pathology. However, gamma-cyto actin provided statistically significant protection against force loss during eccentric contractions. Store-operated calcium entry across the sarcolemma did not differ between mdx fibers compared to wild-type fibers. Additionally, the omission of extracellular calcium or the addition of streptomycin to block stretch-activated channels did not improve the force-generating capacity of isolated extensor digitorum longus muscles from mdx mice during eccentric contractions. CONCLUSIONS: The data presented in this study indicate that upregulation of gamma-cyto actin in dystrophic skeletal muscle can attenuate force loss during eccentric contractions and that the mechanism is independent of activation of stretch-activated channels and the accumulation of extracellular calcium. |
