Myosin molecular motor dysfunction in dystrophic mouse diaphragm

Abstract

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 (x10(9)), 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.