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Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
Published on: November 1, 2012
Skeletal muscle function: role of ionic changes in fatigue, damage and disease
1School of Biomedical Sciences and Institute for Biomedical Research, University of Sydney, Sydney, New South Wales, Australia. davida@physiol.usyd.edu.au
Clinical and Experimental Pharmacology & Physiology
|August 10, 2004
Summary
Early ionic changes in skeletal muscle influence fatigue, stretch-induced damage, and muscular dystrophy. Failure of calcium release contributes to fatigue, while stretch-activated channels affect muscle weakness and disease progression.
Area of Science:
- Muscle physiology and pathophysiology
- Cellular ion dynamics
- Skeletal muscle function
Background:
- Skeletal muscle undergoes functional changes with intense use, including fatigue, soreness after eccentric contractions, and degeneration in disease.
- Ionic shifts within muscle cells play a critical role in these altered states.
- Understanding these early ionic events is key to addressing muscle dysfunction.
Purpose of the Study:
- To investigate the role of early ionic changes in skeletal muscle fatigue, stretch-induced damage, and muscular dystrophy.
- To elucidate the mechanisms underlying muscle weakness and degeneration.
- To explore potential therapeutic targets for muscle disorders.
Main Methods:
- Utilized single mouse muscle fiber preparations with intact tendons for mechanical and ionic measurements.
- Employed fluorescent indicators for simultaneous measurement of intracellular ions and mechanical performance.
- Induced activity changes through electrical stimulation and mechanical stretch.
Main Results:
- Muscle fatigue during repeated activity was primarily linked to impaired calcium release, not intracellular acidosis.
- Eccentric contractions led to increased intracellular calcium (Ca2+) and sodium (Na+), with Na+ influx via stretch-activated channels contributing to muscle weakness.
- In Duchenne muscular dystrophy models (mdx mice), stretch-activated channels facilitate damaging Ca2+ and Na+ increases, and their blockade mitigates some injury.
Conclusions:
- Failure of sarcoplasmic reticulum calcium release is a significant factor in muscle fatigue.
- Stretch-activated ion channels are implicated in stretch-induced muscle damage and Duchenne muscular dystrophy.
- Blocking stretch-activated channels shows promise for mitigating muscle damage in certain disease conditions.
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