Abstract
Muscular dystrophy is a heterogeneous group of hereditary diseases characterized by progressive muscle weakness. In many type of muscular dystrophy, microinjury of the plasma membrane is thought to result in muscle degeneration. However, no model system for inducing microinjury of the muscle plasma membrane and observing its resultant turnover has yet to be reported. To determine whether the muscle cell plasma membrane suffers microinjury and undergoes resultant turnover, we carried out target irradiation of isolated skeletal muscle fibers with heavy ion microbeams.
The effects of heavy ion microbeams on muscle fibers isolated from wild type mouse skeletal muscles were examined by electron microscopy. The plasma membranes of heavy ion beam-irradiated areas of muscle fibers showed
irregular protrusions and invaginations. In the cytoplasm, an irregular distribution of microfilaments was found near the plasma membrane.Sarcoplasmic reticula in the irradiated regions showed a distended appearance with flocculent material within the lumen.Many autophagic vacuoles could be seen at 7 min after irradiation. At 22 min, the vacuoles became more prominent and showed more variety.We also examined the ultrastructural changes of the muscle fibers of SJL mouse, which is a model for human dysferlinopathy (limb-girdle muscular dystrophy type 2B and Miyoshi muscular dystrophy),after irradiation. In addition to the structural changes similar to the wild type, several regions which were thought to be formerly constructed by myofibril, were occupied by the autophagic vacuoles and unidentified membranes. These observations suggest that heavy ion beam irradiation causes disruption of the cellular architecture and the autophagy is involved in removal of this disruption.
