Mechanisms of the suppressing effects of BDM on the actomyosin interaction ; as an experimental model of the muscle fatigue

我们研究了BDM(2，3-丁二酮)抑制肌动球蛋白相互作用的分子机制，并与肌动球蛋白在骨骼肌疲劳过程中的特性进行了比较。使用强同步辐射光源，研究了BDM对活的和有皮肤的骨骼肌纤维中肌球蛋白和肌动蛋白的分子结构的影响。在静息状态下，BDM显著增加了静息赤道强度比。BDM也抑制钙离子激活的收缩，而赤道强度比接近正常收缩的值。BDM还减少了激活过程中经络肌动蛋白层线强度的增加和第二经向肌球蛋白强度的降低，表明BDM主要通过抑制肌动球蛋白相互作用来抑制骨骼肌的收缩。它对赤道反射和肌球蛋白层线的影响小于对肌动蛋白层线的影响，提示BDM影响的肌球蛋白头部可能与肌动蛋白结合，而不遵循肌动蛋白螺旋的对称性。我们还研究了BDM对骨骼肌原纤维缩短的影响。BDM对非负荷缩短率影响不大，但明显减缓了负荷缩短率。BDM的这些效应似乎与疲劳骨骼肌相似，表明BDM处理的肌肉是一种很好的骨骼肌疲劳实验模型。

We investigated the molecular mechanisms of the inhibiting effects of BDM (2, 3-butanedione monoxime) on the actomyosin interaction and compared them with the properties of actomyosin during the skeletal muscle fatigue. Using a strong synchrotron radiation source, the effects of BDM on the molecular structure of myosin and actin in the living and skinned skeletal muscle fibres. In the resting states, BDM significantly increased the resting equatorial intensity ratio. Also BDM suppressed the Ca ion activated contraction, whereas the equatorial intensity ratio was close to the value in normal contraction. BDM also reduced the intensity increase of the meridional actin layer lines and intensity decrease of the second myosin meridional during activation indicating that BDM suppresses the skeletal muscle contraction by mainly inhibiting actomyosin interaction. It has a smaller effect on the equatorial reflections and myosin layer-lines than on the actin layer lines, suggesting that BDM-influenced myosin heads may bind to actin without following the symmetry of the actin helix. We also studied the effects of BDM on the skeletal myofibrils shortening. BDM has little effects on the unloaded shortening, but clearly slowed the loaded shortening. These effects of BDM seems similar to the properties of fatigue skeletal muscles, and indicates BDM treated muscles to be a good experimental model of skeletal muscle fatigue.