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Updated: Aug 30, 2026
Myo-mechanical Analysis of Isolated Skeletal Muscle
Published on: February 22, 2011
Gadolinium reduces short-term stretch-induced muscle damage in isolated mdx mouse muscle fibres
Ella W Yeung1, Stewart I Head, David G Allen
1Institute for Biomedical Research and Department of Physiology, University of Sydney F13, NSW 2006, Australia.
Abstract:
Duchenne muscular dystrophy is a lethal muscle disease caused by absence of the protein dystrophin which is part of a glycoprotein complex located on the intracellular surface of the surface membrane. The precise function of dystrophin and the reason why its absence causes severe muscle damage are unclear. Stretch-induced muscle damage is well recognised in normal muscle and is more severe in muscles from animals lacking dystrophin (mdx mice). It has been proposed that stretch-induced damage underlies the progression of damage in muscular dystrophy. In the present study we confirm that single fibres from mdx muscle are more susceptible to stretch-induced damage and show that there is an associated rise in intracellular sodium concentration ([Na+]i) which is greater than in wild-type mice. We show that this rise in [Na+]i can be prevented by Gd3+, which is an established blocker of stretch-activated channels. mdx fibres have a higher than normal resting [Na+]i and this is also reduced by Gd3+. If Gd3+ is applied over the period in which [Na+]i rises following stretched contraction, it prevents one component of the reduced force. The other component of reduced force is caused by inhomogeneity of sarcomeres and can be minimised by stretching the muscle to its new optimum length. These experiments show that part of the short-term damage caused by stretch in mdx fibres can be prevented by blocking stretch-activated channels.
Insights
Duchenne muscular dystrophy (DMD) muscle fibers show increased stretch-induced damage and sodium influx. Blocking stretch-activated channels with Gd3+ partially prevents this damage, offering a potential therapeutic target for DMD.
Area of Science:
- Biochemistry
- Cell Biology
- Physiology
Background:
- Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle degeneration.
- The absence of dystrophin protein in DMD leads to severe muscle damage, but the exact mechanisms remain unclear.
- Stretch-induced muscle damage is exacerbated in DMD and is a proposed driver of disease progression.
Purpose of the Study:
- To investigate the susceptibility of Duchenne muscular dystrophy (mdx) muscle fibers to stretch-induced damage.
- To determine the role of intracellular sodium concentration ([Na+]i) and stretch-activated channels in this damage.
- To explore potential therapeutic interventions targeting these mechanisms.
Main Methods:
- Single muscle fiber experiments were conducted on mdx mice and wild-type controls.
- Stretch-induced damage and changes in intracellular sodium concentration ([Na+]i) were measured.
- The effects of Gd3+, a blocker of stretch-activated channels, were assessed.
Main Results:
- mdx muscle fibers exhibited greater susceptibility to stretch-induced damage compared to wild-type fibers.
- A significant rise in intracellular sodium concentration ([Na+]i) was observed in mdx fibers following stretch, which was reduced by Gd3+.
- mdx fibers had elevated resting [Na+]i, also reduced by Gd3+.
- Gd3+ partially prevented force reduction following stretched contractions in mdx fibers.
Conclusions:
- Stretch-induced damage in Duchenne muscular dystrophy muscle fibers is associated with increased intracellular sodium influx.
- Stretch-activated channels play a role in the heightened susceptibility of mdx muscle to stretch.
- Blocking these channels with Gd3+ offers a potential strategy to mitigate short-term muscle damage in DMD.
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