Am J Physiol Cell Physiol AJP: Cell Physiology
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Am J Physiol Cell Physiol 277: C1170-C1176, 1999;
0363-6143/99 $5.00
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Vol. 277, Issue 6, C1170-C1176, December 1999

EDITORIAL FOCUS
Myosin molecular motor dysfunction in dystrophic mouse diaphragm

Catherine Coirault1, Francine Lambert1, Sylvain Marchand-Adam1, Pierre Attal2, Denis Chemla3, and Yves Lecarpentier3

1 Institut National de la Santé et de la Recherche Médicale U451-LOA-Ensta-Ecole Polytechnique, 91761 Palaiseau Cedex; and Services 2 d'ORL and 3 d'Explorations Fonctionnelles Cardiovasculaires et Respiratoires, Centre Hospitalier et Universitaire de Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France

Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) and mdx (n = 12) mice. Compared with control, peak tetanic tension fell by 50% in mdx mice (P < 0.001). The total number of cross bridges per square millimeter (×109), the elementary force per cross bridge, and the peak mechanical efficiency were lower in mdx than in control mice (each P < 0.001). The duration of the cycle and the rate constant for cross-bridge detachment were significantly lower in mdx than in control mice. In the overall population, there was a linear relationship between peak tetanic tension and either total number of cross bridges per square millimeter or elementary force per cross bridge (r = 0.996 and r = 0.667, respectively, each P < 0.001). The mdx mice presented a higher proportion of type IIA MHC (P < 0.001) than control mice and a reduction in type IIX MHC (P < 0.001) and slow myosin isoforms (P < 0.01) compared with control mice. We concluded that, in mdx mice, impaired diaphragm strength was associated with qualitative and quantitative changes in myosin molecular motors. It is proposed that reduced force generated per cross bridge contributed to diaphragm weakness in mdx mice.

mdx mice; cross bridge; muscle efficiency; skeletal muscle


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