肌球蛋白抑制剂BDM对骨骼肌收缩功能的非特异性作用

目的:探讨萎缩骨骼肌单位面积上等长收缩最大张力(Pt)降低的机理.方法:采用肌球蛋白ATP酶抑制剂BDM(Butanedione monoxime)灌流,观测其对离体骨骼肌肌条等长收缩功能的影响.结果:研究表明,BDM可使比目鱼肌(SOL)与趾长伸肌(EDL)等长收缩Pt明显降低,BDM对骨骼肌收缩功能的抑制呈剂量依赖性关系,且完全可逆.低浓度BDM(1 mmol/L)仅降低骨骼肌等长收缩的Pt而不影响其收缩时程,高浓度(10 mmol/L)下使收缩时程明显缩短.与SOL相比,在10mmol/LBDM作用下,使EDL等长收缩Pt降低一半的时间明显加快.无论在低浓度还是高浓度下,BDM对EDL肌球蛋白ATP酶活性的抑制作用均大于SOL.在相同浓度下,BDM对Pt的抑制程度远远大于对肌球蛋白ATP酶活性的抑制.结论:这些结果提示骨骼肌横桥功能降低可能是其等长收缩pt下降的原因之一;BDM并非特异型肌球蛋白ATP酶抑制剂,可对兴奋-收缩偶联的多个环节产生影响.

Non-specific effect of myosin inhibitor BDM on skeletal muscle contractile function

Aim: In order to elucidate the underlying mechanism of depressed maximal isometric twitch tension normalized by cross sectional area of muscle strip in unloaded soleus.Methods: The soleus and extensor digitorum longus(EDL) muscle strips were perfused in vi(tro) and treated by 2,3-Butanedione monoxime(BDM).Results: The BDM decreased Pt of soleus and EDL in a concentration-dependent manner.The Pt could restored completely to normal level after washing out BDM.The isometric twitch duration was not altered during 1 mmol/L BDM of perfusion,but was shortened at 10 mmol/L dose.The time from maximal to half Pt in EDL was shorter than that in soleus during 10 mmol/L BDM of perfusion.The inhibitory effects of BDM on myosin ATPase activity were higher in EDL than in soleus.The inhibitory extent of BDM on myosin ATPase activity of soleus and EDL was lower than that on Pt.Conclusion: These results suggest that reduction in cross-bridge function of skeletal muscle may be one of reasons induced a decrease in its Pt.BDM is not a specific inhibitor on myosin ATPase activity and can affect multiple parts of excitation-contraction coupling in skeletal muscle.