Fiber Myosin Heavy Chain Polymorphism is Associated with a Heightened Susceptibility to Eccentric Damage

Abstract

The purpose of this study was to model the relationship between fiber myosin heavy chain (MHC) isoform content and susceptibility to damage by a standardized eccentric contraction (+25% change in fiber length; 50% of unloaded shortening velocity, Vo). Damage was quantified as the pre- to post-eccentric change in Ca2+-activated force. Chemically skinned fibers from the soleus and EDL of C57BL/6 mice were studied in order to obtain MHC monomorphic (type I, IIa, IIx, IIb) and polymorphic (I/IIa, IIa/IIx, IIx/IIb) fibers. Fiber MHC isoform content was determined by SDS-PAGE. The mean (±SE) pre- to post-eccentric change in force was −5.2 ± 0.5 kN/m2 (n = 24) for type I fibers, −18.3 ± 1.5 (7) for I/IIa, −5.3 ± 0.7 (27) for IIa, −18.1 ± 2.3 (5) for IIa/IIx, −5.4 ± 0.6 (34) for IIx, −17.8 ± 1.1 (11) for IIx/IIb, and −5.7 ± 0.8 (24) for IIb. Multiple linear regression indicated that, independent of MHC content, greater pre-specific force was associated with a slightly greater post-force deficit (slope = 0.94). With pre-eccentric force held constant, no relationship was found between fiber Vo and post-eccentric force (p = 0.716) . In contrast, data were well described by a model using pre-eccentric force and MHC polymorphism as predictors (p < 0.001; r2 = 0.97): post-force of monomorphic fibers = 0.94(pre-force) + 2.04 kN/m2 post-force of polymorphic fibers = 0.94(pre-force) - 12.15 kN/m2 The significant difference (p < 0.001) in model y-intercepts reveals that, at similar pre-eccentric specific force, MHC polymorphism was associated with a 14 kN/m2 greater eccentric-induced reduction in force vs. monomorphic fibers. We conclude that MHC polymorphism is associated with a heightened sensitivity to high mechanical strain at the level of the myofilament lattice or cytoskeleton.