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Rate of force recovery immediately following lengthening contractions for various mouse models of muscular dystrophy
Author(s) -
Rader Erik Paul,
Han Renzhi,
Levy Jennifer R.,
Bansal Dimple,
Campbell Kevin P.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1141.6
Subject(s) - dysferlin , sarcolemma , dystrophin , muscular dystrophy , dystroglycan , chemistry , microbiology and biotechnology , extensor digitorum longus muscle , skeletal muscle , biology , extracellular matrix , anatomy , genetics , laminin
Mutations in genes encoding distinct proteins of the dystrophin‐glycoprotein complex (DGC) or dysferlin are associated with various forms of muscular dystrophy. Dystrophin, β‐sarcoglycan, and glycosylated α‐dystroglycan are essential components of the DGC which links the extracellular matrix to the cytoskeleton and prevents extreme sarcolemma damage. Dysferlin also helps to maintain sarcolemma integrity but by a different mechanism – membrane repair. Muscle fibers with either hypoglycosylated α‐dystroglycan or dysferlin deficiency have an inability to reseal laser‐induced sarcolemma damage. To what extent compromised resealing correlates with force generation after contraction‐induced injury is unclear. We tested the hypothesis that hypoglycosylated α‐dystroglycan or deficiency in dysferlin, dystrophin, or β‐sarcoglycan is associated with a slow rate of force recovery immediately following a lengthening contraction protocol (LCP). The extensor digitorum longus muscle was isolated, exposed to a LCP, and monitored at various time points for up to 45 minutes post‐LCP. Muscles with hypoglycosylated α‐dystroglycan or deficiency in dystrophin or β‐sarcoglycan sustained slow rates of force recovery. Muscles of dysferlin‐null mice exhibited wild‐type recovery rates. Interestingly, muscles of mice deficient in both dystrophin and dysferlin exhibited rate constants of recovery (0.032 ± 0.012 min −1 ) significantly lower than those for muscles null for dystrophin alone (0.080 ± 0.006 min −1 ). This indicated that a disrupted DGC unmasks the function of dysferlin in force recovery. Determining the rate of force recovery may be a useful method for evaluating the physiological consequences of impaired sarcolemma resealing in various mouse models of muscular dystrophy.