The occurrence of contraction-induced lesions in the sarcolemma of skeletal muscles: Insights from a micro-sized whole muscle model

[摘要] Muscles exposed to unaccustomed exercise or injurious contractile activities are likely to sustain mechanical damage to muscle fibers, a characteristic of contraction-induced injuries. The susceptibility of muscles to contraction-induced injury increases with age, disuse or disease. Although lesions in the sarcolemma have been implicated in the injury process, the conditions that lead to the formation of such lesions, as well as the extent to which these lesions affect muscle function remain inadequately understood. To study membrane-based events reliably, we developed a micro-sized whole muscle model that was robust, but more importantly, compatible with the contemporary techniques used to study cellular function. In characterizing this muscle model in vitro, we report a level of stability and flexibility that had not been observed in previous whole muscle preparations. Utilizing this muscle model, we demonstrated that sarcolemmal lesions and overactive mechanosensitive ion channels accounted for the majority of the functional deficit observed in the diseased muscles of mdx mice, the murine model of Duchenne Muscular Dystrophy. These results provide a basis for the development of therapeutic strategies directed at stabilizing the membrane of dystrophic skeletal muscle. When wild-type muscles were subjected to an injurious protocol of lengthening contractions, the mechanical stress associated with lengthening contractions, while severe enough to cause a 30% force deficit, was found to be insufficient to elicit membrane lesions in a whole skeletal muscle. This finding diminished the role of mechanical stress as the direct cause of sarcolemmal injury and implies that contraction-induced lesions observed in wild-type muscle are likely to result from the contributions of other factors, such as reactive oxygen species and proteolytic enzyme activity.

[发布机构] University of Michigan

[效力级别] Contraction-induced Injury

[关键词] Skeletal Muscles;Contraction-induced Injury;Biomedical Engineering;Engineering;Biomedical Engineering