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This Article Full Text Full Text (PDF) All Versions of this Article: 89/5/531    most recent expphysiol.2004.027383v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Head, S. I. Articles by Liangas, G. Search for Related Content PubMed PubMed Citation Articles by Head, S. I. Articles by Liangas, G. Related Collections Muscle

¹ School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia and² School of Biomedical & Chemical Sciences, University of Western Australia, WA, 6009, Australia

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/dy^2j, dystrophia muscularis, dystrophic mouse, in which the laminin-₂ component of the dystrophin-associated complex is mutated, to test the hypothesis that the disruption of this complex will destabilize the lipid bilayer, rendering it more susceptible to damage during eccentric contractions. We demonstrated that neither slow- nor fast-twitch dystrophic muscles were more susceptible to eccentric contractions when compared with controls. Only fast-twitch extensor digitorum longus (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 bilayer 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 contraction damage. The C57BL6J/dy^2j dystrophic laminopathy produced the 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 contributed to the reduction in maximal force in the dystrophic muscles. We conclude that our data do not support the structural hypothesis that the dystrophin-associated complex acts as a scaffolding to support the lipid bilayer, but are consistent with channel-based hypotheses put forward to explain the dystrophic process.

(Received 5 February 2004; accepted after revision 14 May 2004; first published online 7 June 2004)
Corresponding author S. I. Head: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Email: s.head{at}unsw.edu.au

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