Inhibition of contraction of cultured muscle fibers results in increased turnover of myofibrillar proteins but not of intermediate-filament proteins.

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Abstract
Muscle fibers [rabbit] are maintained in culture in a fully contractile state and are relaxed by the addition of 10-7 M tetrodotoxin (TTX). This toxin binds to muscle membrane Na+-channels, abolishes spontaneous contractions and causes failure of the fiber to accumulate myosin H chains. These effects are reversible on removal of TTX. Synthesis and accumulation kinetics were obtained for myofibrillar and for cytoplasmic filament proteins in normal, active muscle and in TTX-relaxed muscle fibers in culture. In relaxed fibers, the synthesis of most proteins remained normal or slightly elevated. The accumulation of all myofibrillar proteins examined was markedly inhibited in TTX-treated cultures; the accumulation of cytoplasmic filament proteins was normal or slightly elevated. Myofibrillar proteins examined were .alpha.-actin, troponin-C, myosin fast L chain 1, myosin fast L chain 2, .alpha.,.beta.-tropomyosins and the phosphorylated forms of tropomyosin and fast L chain 2. Cytoplasmic filament proteins studied were vimentin, .alpha.,.beta.-desmin and .beta.,.alpha.-actin. The synthesis and accumulation of 6 unidentified muscle-specific proteins and 9 unidentified nonmuscle-specific proteins were examined. Most of these proteins showed a normal accumulation pattern in TTX-relaxed fibers. Muscle fibers made inactive by TTX display an increased instability of all myofibrillar proteins while cytoplasmic filament proteins and cytoplasmic proteins in general are relatively unaffected. TTX interferes, in a manner as yet unidentified, with assembly and normal stability of myofibrils. Decreased assembly and/or increased instability of myofibrils would lead to increased rates of myofibrillar protein degradation.