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Membrane alterations in skeletal muscle fibers of dystrophic mice
Abstract:
Skeletal muscle fibers from dystrophic mice and littermate controls (ReJ-129) were characterized electrically and then injected with an intracellular marker. In this way they could be identified for examination with an electron microscope to correlate the relative time course of electrical and ultrastructural alterations resulting from the dystrophic process. On the average, dystrophic muscle fibers displayed decreased membrane potentials (-59 +/- 1.2 vs -79 +/- 0.7 mV for normals), decreased specific membrane resistivity (517 +/- 27 vs 642 +/- 34 omega-cm2 for normals), and depressed action potential (AP) maximum rates of rise (+Vmax) (352 +/- 9 vs 417 +/- 9 V/s for normals) and amplitudes (92 +/- 1.2 vs 102 +/- 1.0 mV for normals) at an experimentally polarized membrane potential of -90 mV. Membrane resistivity and AP +Vmax were decreased even in those fibers from dystrophic muscles that displayed normal ultrastructure (classified visually and by ratio of sarcoplasmic reticulum to total cell volume). These findings support the membrane hypothesis of muscular dystrophy that membrane lesions are the primary lesion in the disease process.
Insights
Dystrophic muscle fibers show electrical abnormalities, including reduced membrane potential and action potential rise rate, even with normal structure. These findings support the membrane theory of muscular dystrophy.
Area of Science:
- Biophysics
- Cell Biology
- Neuroscience
Background:
- Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness and degeneration.
- The underlying mechanisms of muscular dystrophy, particularly the role of cell membrane integrity, are not fully understood.
Purpose of the Study:
- To investigate the electrical and ultrastructural characteristics of skeletal muscle fibers in dystrophic mice.
- To correlate the temporal relationship between electrical and ultrastructural changes in muscular dystrophy.
- To evaluate the validity of the membrane hypothesis of muscular dystrophy.
Main Methods:
- Skeletal muscle fibers were isolated from dystrophic mice and control littermates.
- Electrical properties (membrane potential, specific membrane resistivity, action potential characteristics) were measured.
- Intracellular markers were used for fiber identification.
- Electron microscopy was employed to examine ultrastructure.
Main Results:
- Dystrophic muscle fibers exhibited significantly decreased membrane potentials and specific membrane resistivity compared to controls.
- Action potential maximum rates of rise (+Vmax) and amplitudes were depressed in dystrophic fibers.
- Electrical alterations were observed even in dystrophic fibers with normal ultrastructure.
Conclusions:
- The study provides strong support for the membrane hypothesis of muscular dystrophy.
- Primary membrane lesions are implicated as the cause of the dystrophic process.
- Early electrical changes in muscle fibers may precede observable ultrastructural damage.