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• W2945165554 endingPage "C234" @default.
• W2945165554 startingPage "C226" @default.
• W2945165554 abstract "Limb-girdle muscular dystrophy 2i (LGMD2i) is a dystroglycanopathy that compromises myofiber integrity and primarily reduces power output in limb muscles but can influence cardiac muscle as well. Previous studies of LGMD2i made use of a transgenic mouse model in which a proline-to-leucine (P448L) mutation in fukutin-related protein severely reduces glycosylation of α-dystroglycan. Muscle function is compromised in P448L mice in a manner similar to human patients with LGMD2i. In situ studies reported lower maximal twitch force and depressed force-velocity curves in medial gastrocnemius (MG) muscles from male P448L mice. Here, we measured Ca 2+ -activated force generation and cross-bridge kinetics in both demembranated MG fibers and papillary muscle strips from P448L mice. Maximal activated tension was 37% lower in MG fibers and 18% lower in papillary strips from P448L mice than controls. We also found slightly faster rates of cross-bridge recruitment and detachment in MG fibers from P448L than control mice. These increases in skeletal cross-bridge cycling could reduce the unitary force output from individual cross bridges by lowering the ratio of time spent in a force-bearing state to total cycle time. This suggests that the decreased force production in LGMD2i may be due (at least in part) to altered cross-bridge kinetics. This finding is notable, as the majority of studies germane to muscular dystrophies have focused on sarcolemma or whole muscle properties, whereas our findings suggest that the disease pathology is also influenced by potential downstream effects on cross-bridge behavior." @default.
• W2945165554 created "2019-05-29" @default.
• W2945165554 creator A5004604138 @default.
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• W2945165554 date "2019-08-01" @default.
• W2945165554 modified "2023-09-26" @default.
• W2945165554 title "Demembranated skeletal and cardiac fibers produce less force with altered cross-bridge kinetics in a mouse model for limb-girdle muscular dystrophy 2i" @default.
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• W2945165554 doi "https://doi.org/10.1152/ajpcell.00524.2018" @default.
• W2945165554 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31091146" @default.
• W2945165554 hasPublicationYear "2019" @default.
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