Reversible oxidative modifications partially cause myofibrillar active and passive force decline in early phase of immobilization.

Abstract

Muscle immobilization leads to a decrease in muscle fiber size and contractile function, partly due to a decline in myofibrillar force. In this study, we examined the effects of reversible oxidative modifications on the decline of myofibrillar function during the early phase of immobilization. One leg of male C57BL6 mice was immobilized for 3 days and 7 days, whereas the contralateral leg was used as a nontreated (NT) control. After the given immobilization periods, mechanically skinned fibers were prepared from the gastrocnemius muscle, and myofibrillar active and passive forces were assessed. Myofibrillar specific force decreased after 7 days of immobilization, although myofibrillar Ca²⁺ sensitivity remained unchanged. The decreased specific force was partially restored by a treatment with dithiothreitol (DTT), a reducing agent, only when applied to nonactivated fibers, not activated fibers. In addition, 3-morpholinosydnonimine and peroxynitrite (ONOO^-) decreased maximal force in nonactivated fibers from NT but not immobilized (Im) muscles. Myofibrillar passive force decreased after 7 days of immobilization. DTT treatment increased passive force in both NT and Im fibers, with a greater improvement seen in Im fibers. Furthermore, treatment with oxidized glutathione before DTT treatment decreases passive force in both NT and Im fibers, with a greater reduction seen in NT fibers. These results suggest that reversible oxidative modifications partially contribute to the impairments in both myofibrillar active and passive forces, at least in the early phase of immobilization. Specifically, ONOO^- and S-glutathionylation likely play an important role in active and passive force, respectively.NEW & NOTEWORTHY Muscle disuse negatively affects muscle quality, in part due to an impairment of myofibril. This study was the first to reveal that reducing treatment can partially restore the decreased myofibrillar maximal force and passive force observed during the early phase of immobilization. Furthermore, the results suggest that peroxynitrite-induced modification and S-glutathionylation of titin likely contribute to the decreases in active and passive forces, respectively. This study provides valuable insights for the population affected by muscle immobilization.