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Are hypercontracted muscle fibers artifacts and do they cause rupture of the plasma membrane?
Abstract:
Muscle fibers with hypercontracted zones (contractures) and plasma membrane defects are relatively frequent in Duchenne dystrophy, but artifacts might account for either. To investigate the problem further, we determined the frequency of hypercontracted muscle fibers in longitudinal, trichrome-stained paraffin sections in 143 muscle biopsy specimens in a wide variety of muscle diseases. The specimens were held at rest length during fixation. The incidence of hypercontracted fibers in Duchenne dystrophy was significantly higher than in any of the other diseases or in normal controls. We also induced contractures in rat muscle by fixation without restraint, electrical stimulation, and cutting the muscle fibers in vivo. Electron-microscopy showed no plasma membrane defects associated with the contractures, except in the cut fibers within 25 micron of their cut ends, which were probably overloaded with calcium. The results indicate that (1) in Duchenne dystrophy the contractures in muscle fibers held at rest length during fixation cannot be accounted for by artifact; (2) contractures occurring in normal muscle during fixation do not in and of themselves cause rupture of the muscle fiber plasma membrane.
Insights
Hypercontracted muscle fibers are common in Duchenne muscular dystrophy and not due to artifacts. These contractures in muscle fibers do not cause plasma membrane defects in normal muscle.
Area of Science:
- Muscle biology
- Pathology
- Biochemistry
Background:
- Hypercontracted zones (contractures) and plasma membrane defects are frequently observed in Duchenne muscular dystrophy (DMD) muscle fibers.
- It remains unclear whether these findings are genuine pathological features or experimental artifacts.
Purpose of the Study:
- To investigate the incidence of hypercontracted muscle fibers in Duchenne muscular dystrophy compared to other muscle diseases and normal controls.
- To determine if artifactual contractures can cause plasma membrane defects.
Main Methods:
- Analysis of 143 muscle biopsy specimens from various muscle diseases using longitudinal, trichrome-stained paraffin sections.
- Muscle specimens were fixed at rest length.
- Induction of contractures in rat muscle via fixation without restraint, electrical stimulation, and in vivo cutting of muscle fibers, followed by electron microscopy.
Main Results:
- The incidence of hypercontracted muscle fibers was significantly higher in Duchenne muscular dystrophy compared to other diseases and normal controls.
- Electron microscopy revealed no plasma membrane defects associated with artifactually induced contractures, except near cut ends of fibers.
- Cut muscle fibers showed calcium overload near the cut ends, suggesting localized damage.
Conclusions:
- Hypercontracted muscle fibers in Duchenne muscular dystrophy, when fixed at rest length, are not artifacts.
- Artifactual contractures in normal muscle do not inherently cause plasma membrane rupture.