Properties of enzymatically isolated skeletal fibres from mice with muscular dystrophy.

摘要

1. Single intact muscle fibres were enzymatically isolated from the skeletal muscles of the dystrophic mouse 129/ReJ dy/dy and were subjected to a range of physiological interventions. 2. Electrophysiological measurements, diffusion of injected dyes (Lucifer Yellow), microdissection and general appearance in the light microscope have shown that the majority of skeletal fibres isolated from the soleus and extensor digitorum longus (EDL) of adult dystrophic mice (10-14 weeks old) had gross morphological abnormalities. These abnormalities ranged from simple branching of the fibre to interconnections of many fibre branches which form a complex syncitium. 3. Segments from fibres of normal appearance and from fibres with morphological deformities were chemically skinned with Triton X-100 and activated in Ca2(+)- and Sr2(+)-buffered solutions. The different characteristics of the Ca2(+)- and Sr2(+)-activation curves were also used to identify the fibre type. 4. Gross morphological abnormalities were observed both in fibres which had predominantly slow-twitch and fast-twitch characteristics. 5. A new group of fibres was found to exist in the soleus muscle of dystrophic animals and represented about 18% of the entire soleus fibre population. This group of fibres had predominantly fast-twitch characteristics and some of these fibres were also grossly malformed. 6. The activation characteristics of individual branches from the same complex syncitium were similar, indicating that the contractile and regulatory proteins were of one type in one syncitium. 7. Chemically skinned segments from malformed fibres which included a major deformity between the points of attachment were generally unable to sustain near-maximal forces. 8. The proportion of malformed fibres which remained intact decreased markedly after prolonged tetanical stimulation of the intact muscle. This strongly suggests that malformed fibres are also functionally weak and prone to progressive damage when stimulated within the intact muscle. 9. The presence in large proportions of fibres with gross morphological abnormalities may explain the symptoms of severe and progressive muscle weakness and muscle loss which are apparent in the 129/ReJ dy/dy mice and possibly even in the human dystrophies such as Duchenne muscular dystrophy.