Molecular and cellular contractile dysfunction of dystrophic muscle from young mice

Dawn A. Lowe, Brian O. Williams, David D. Thomas, Robert W. Grange

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The purpose of this study was to determine whether contractile protein alterations are responsible for force deficits in young dystrophic muscle. Contractility of intact extensor digitorum longus muscles and permeabilized fibers from wild-type (wt), dystrophin-deficient (mdx), and dystrophin/utrophin- deficient (mdx:utrn-/-) mice aged 21 and 35 days was determined. Myosin structural dynamics were assessed by site-directed spin labeling and electron paramagnetic resonance spectroscopy. The principal finding was that force generation was depressed by ∼20% in mdx muscles, but fiber Ca 2+-activated force and myosin structure were not different from wt animals, suggesting that contractile proteins are not responsible for the force deficits in those muscles. For mdx:utrn-/- mice, muscle and fiber forces were ∼40% lower than wt and the fraction of strong-binding myosin during contraction was reduced by 13%. These data indicate that contractile protein alterations, in addition to myosin dysfunction, cause force deficit in muscles from young mdx:utrn-/- mice. Elucidating the molecular mechanisms underlying muscle weakness at the onset of disease is important for designing treatment strategies.

Original languageEnglish (US)
Pages (from-to)92-100
Number of pages9
JournalMuscle and Nerve
Volume34
Issue number1
DOIs
StatePublished - Jul 2006

Keywords

  • Duchenne muscular dystrophy
  • Electron paramagnetic resonance spectroscopy
  • Force deficit
  • Myosin
  • mdx mouse

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