Received February 5, 2004
Revised March 9, 2004
Accepted after revision May 14, 2004
EDL and soleus muscles of the C57BL6J/dy2j laminin-a2 deficient dystrophic mouse are not vulnerable to eccentric contractions
Stewart I Head 1*,
Anthony J Bakker 2,
Georgios Liangas 1
1 University of New South Wales
2 University of Western Australia
* To whom correspondence should be addressed. E-mail: s.head{at}unsw.edu.au.
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Abstract |
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Many muscular dystrophies arise as a consequence of mutations in a series of interconnected proteins associated with the sarcolemma. This group of proteins is collectively referred to as the dystrophin associated complex. We used the C57BL6J/dy2j, dystrophia muscularis, dystrophic mouse, in which the laminin-a2 component of the dystrophin associated complex is mutated, to test the hypothesis that the disruption of this complex will destabilise the lipid bi-layer rendering it more susceptible to damage during eccentric contractions. We demonstrated that neither slow- or fast- twitch dystrophic muscles were more susceptible to eccentric contractions when compared with controls. Only fast-twitch EDL muscles (from both dystrophic and control mice) showed an irreversible loss of force with our eccentric contraction protocol, suggesting that it is the fast 11b fibres (not present in slow- twitch soleus) which are most susceptible to eccentric damage. We used the general anaesthetic Halothane to increase the fluidity of the lipid bi-layer to see if this would uncover any greater susceptibility of the dystrophic muscle to eccentric damage. This also did not reveal any greater fragility of fast- and slow- twitch dystrophic muscles We did, however, demonstrate that Halothane made both control and dystrophic fast- and slow- twitch muscles more susceptible to eccentric contractions. The C57BL6J/dy2j dystrophic laminopathy had pathophysiological and pathohistological characteristics associated with muscular dystrophy: the fast- and slow- twitch dystophic muscles produced only 55% and 53% respectively, of the force of control muscles and 34% and 40%, respectively, of the dystrophic muscle fibres were branched. The presence of the branched fibres in the dystrophic muscles did not make them more susceptible to eccentric damage but may have contribute to the reduction in maximal force in the dystrophic muscles. We conclude that our data does not support the structural hypothesis that the dystrophin associated complex acts as a scaffolding to support the lipid bi-layer. but, is consistent with channel-based hypotheses put forward to explain the dystrophic process.
Key Words:
Muscle contraction, Muscle fibre, Muscular dystrophy
