Myosin molecular motor dysfunction in dystrophic mouse diaphragm

C Coirault, F Lambert… - … of Physiology-Cell …, 1999 - journals.physiology.org
C Coirault, F Lambert, S Marchand-Adam, P Attal, D Chemla, Y Lecarpentier
American Journal of Physiology-Cell Physiology, 1999journals.physiology.org
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 …
Cross-bridge properties and myosin heavy chain (MHC) composition were investigated in isolated diaphragm from 6-mo-old control (n = 12) andmdx(n = 12) mice. Compared with control, peak tetanic tension fell by 50% inmdx 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 (eachP < 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 andr = 0.667, respectively, eachP < 0.001). Themdx 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, inmdx 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 inmdx mice.
American Physiological Society