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

DS Gokhin, NE Kim, SA Lewis… - … of Physiology-Cell …, 2012 - journals.physiology.org
DS Gokhin, NE Kim, SA Lewis, HR Hoenecke, DD D'Lima, VM Fowler
American Journal of Physiology-Cell Physiology, 2012journals.physiology.org
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 (∼ 1.65 μm), 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 …
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 (∼1.65 μm), 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 ± 0.08 to 1.37 ± 0.04 μm, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 μm further from the Z-line than the NH2-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulin-free, pointed-end extensions that comprise up to 34% of total thin-filament 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.
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