Thin-filament length correlates with fiber type in human skeletal muscle

Abstract

Fowler VM. Thin-filament length correlates with fiber type in human skeletal muscle. Am J Physiol Cell Physiol 302: C555-C565, 2012. First published November 9, 2011; doi:10.1152/ajpcell.00299.2011.-Force production in skeletal muscle is proportional to the amount of overlap between the thin and thick filaments, which, in turn, depends on their lengths. Both thin-and thick-filament lengths are precisely regulated and uniform within a myofibril. While thick-filament lengths are essentially constant across muscles and species (ϳ1.65 m), thin-filament lengths are highly variable both across species and across muscles of a single species. Here, we used a high-resolution immunofluorescence and image analysis technique (distributed deconvolution) to directly test the hypothesis that thin-filament lengths vary across human muscles. Using deltoid and pectoralis major muscle biopsies, we identified thin-filament lengths that ranged from 1.19 Ϯ 0.08 to 1.37 Ϯ 0.04 m, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 m further from the Z-line than the NH2-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulinfree, pointed-end extensions that comprise up to 34% of total thinfilament length. Furthermore, thin-filament length was negatively correlated with the percentage of type 2X myosin heavy chain within the biopsy and shorter in type 2X myosin heavy chain-positive fibers, establishing the existence of a relationship between thin-filament lengths and fiber types in human muscle. Together, these data challenge the widely held assumption that human thin-filament lengths are constant. Our results also have broad relevance to musculoskeletal modeling, surgical reattachment of muscles, and orthopedic rehabilitation.actin; length-tension curve; myosin heavy chain; nebulin; tropomodulin FORCE GENERATION IN SKELETAL muscle arises from cross-bridge interactions between myosin (thick) filaments and actin (thin) filaments in the sarcomeres of the myofibrillar lattice. A sarcomere's force-generating capacity is described by the sliding filament model, which states that the degree of myofilament overlap determines the amount of force that can be actively produced (25). Therefore, myofilament lengths are among the chief determinants of the shape of the length-tension curve (13,19,46,56), which quantitatively describes a sarcomere's force output as a function of myofilament overlap and establishes a sarcomere's operating length range (9,17,18,24,56). Myofilaments are polymeric, but their lengths are strictly controlled during sarcomere assembly and maintenance and are highly uniform within a myofibril (38). Given that whole muscle contractile performance can be accurately predicted from sarcomere-level myofilament geometry (58), obtaining high-resolution measurements of myofilament lengths in human muscles to construct muscle-specific, length-tension relationships has profound clinical significance. For example, accurate length-tension propertie...

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