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- W2912409132 abstract "Duchene muscular dystrophy (DMD) is a genetic disorder resulting in the absence of dystrophin and progressive muscle degeneration and weakness. Dystrophin is a part of the costamere complex that links the contractile apparatus with the cytoskeleton and sarcolemma membrane of muscle cells. To determine how a lack of dystrophin affects the structure and function of the contractile apparatus we used time resolved X-ray diffraction in relaxed muscle and during contraction-relaxation of intact extensor digitorum longus (EDL) muscles. EDL muscle bundles were isolated from 9- and 11-month-old DMD and WT rats. Twitch and tetanic (100 Hz stimulation) force of DMD muscle was significantly less compared to age-matched WT muscle. Additionally, DMD muscle had prolonged relaxation in twitch measurements and slower activation and relaxation for tetanic contraction. Interestingly, an 11-month-old DMD rat presented more severe muscle weakness and slower contractile kinetics compared to the 9-month-old DMD muscle. The time-resolved structure from X-ray imaging revealed increased average lattice spacing (d1,0) at rest and throughout activation for DMD muscle. The I1,1/I1,0 intensity ratio was significantly lower in 9-month-old DMD muscle at rest and during activation and this was further decreased in 11-months-old muscles. Interestingly, the rate of change of intensity ratio did not differ between DMD and WT EDL during contraction or relaxation. The dynamics of change in the first-order myosin layer line (MLL1) intensity, a measure of order/disorder in crossbridge distribution along thick filaments, varied between EDL of DMD vs WT rats but was not significantly different. Thus our preliminary results demonstrate that DMD skeletal muscle produces weaker, slower contractions, associated with contractile lattice expansion and reduced movement of myosin towards thin filaments during isometric contraction. Supported by R01HL128368." @default.
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- W2912409132 date "2019-02-01" @default.
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- W2912409132 title "Time-Resolved X-Ray Studies of Skeletal Muscle from a Duchene Muscular Dystrophy Rat Model" @default.
- W2912409132 doi "https://doi.org/10.1016/j.bpj.2018.11.2183" @default.
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