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Isometric and Eccentric Force Generation Assessment of Skeletal Muscles Isolated from Murine Models of Muscular Dystrophies
Published on: January 31, 2013
Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy
Saskia Lassche1, Ger J M Stienen, Tom C Irving
1Department of Neurology, Neuromuscular Centre Nijmegen, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. s.lassche@neuro.umcn.nl
Neurology
|February 1, 2013
Summary
Facioscapulohumeral muscular dystrophy (FSHD) causes muscle weakness due to reduced sarcomeric force in type II muscle fibers. Titin stiffening may compensate for this dysfunction.
Area of Science:
- Muscle physiology
- Molecular biology
- Genetics
Background:
- Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by progressive muscle weakness.
- The underlying mechanisms of muscle weakness in FSHD are not fully understood.
- Sarcomeric dysfunction is a potential contributor to muscle weakness in various muscular dystrophies.
Purpose of the Study:
- To investigate the role of sarcomeric dysfunction in muscle weakness observed in FSHD.
- To compare sarcomeric function between FSHD patients and healthy individuals.
Main Methods:
- Contractile studies on demembranated single muscle fibers from quadriceps biopsies.
- Measurement of force-length relationships, thin filament length, and myofilament lattice spacing.
- Utilized immunofluorescence confocal microscopy and X-ray diffraction.
Main Results:
- FSHD muscle fibers exhibited reduced active force (70% of controls), specifically in type II fibers.
- No significant changes in thin filament or sarcomere length were observed.
- Increased passive force and calcium sensitivity, with decreased myofilament lattice spacing, suggest titin compensation.
Conclusions:
- Sarcomeric dysfunction, characterized by reduced force in type II fibers, is evident in FSHD.
- Titin stiffening appears to be a compensatory mechanism.
- Sarcomeric dysfunction is proposed as a critical factor in FSHD-related muscle weakness.
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