J Physiol ：科学家找到导致肌无力的新变异

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　　J Physiol ：科学家找到导致肌无力的新变异 ??在发表于最新一期的《TheJournalofPhysiology》上的文章中，科学家确认了一种新型变异和肌无力以及肢端畸形等症状有关。这一研究证实了由于原肌球蛋白变异导致肌无力的病人其病因和一种内在的机制有关，该机制使得原肌球蛋白的收缩速度和产生力量的能力发生了变化。??来自瑞典Uppsala大学的临床神经生理学系的JulienOchala博士和同事通过与Goteborg大学病理学系的科学家们   生物谷：在发表于最新一期的《The Journal of Physiology》上的文章中，科学家确认了一种新型变异和肌无力以及肢端畸形等症状有关。这一研究证实了由于原肌球蛋白变异导致肌无力的病人其病因和一种内在的机制有关，该机制使得原肌球蛋白的收缩速度和产生力量的能力发生了变化。

  来自瑞典Uppsala大学的临床神经生理学系的Julien Ochala博士和同事通过与Goteborg大学病理学系的科学家们合作，分析了一位妇女及她女儿的肌无力的内在机制，该妇女以及她的女儿都发生了β原肌球蛋白变异。

  在研究中针对单个肌纤维的收缩力测试以及对于运动力的分析证实，存在原肌球蛋白对于肌浆球蛋白——肌动蛋白之间动力学的影响机制。正是由于存在这种原肌球蛋白变异，将造成肌浆球蛋白和肌动蛋白结合速率变慢，而两者的分离速率则变快。这最终将导致只有少量的肌浆球蛋白分子能和肌动蛋白紧密结合，从而形成肌无力的症状。研究结果同时还反映出原肌球蛋白在生理学上影响肌肉的收缩速度以及产生力的能力方面存在作用。

  这一研究结果意味着，以上在基因、蛋白和肌细胞水平上的神经肌肉紊乱症状对于我们了解疾病发生原因有着重要意义，并且将可能带来新的治疗肌无力等疾病的手段。科学家Walter R. Frontera表示：“Ochala博士和他的同事很好的证明了在这两者之间存在的联系。” （引自教育部科技发展中心）

??英文原文链接：http://www.physorg.com/news101046096.html



原始出处:

J Physiol 2007 581: 1283-1292. First Published online on April 12, 2007

SKELETAL MUSCLE AND EXERCISE

Effects of a R133W -tropomyosin mutation on regulation of muscle contraction in single human muscle fibres

Julien Ochala1, Mingxin Li1,2, Homa Tajsharghi3, Eva Kimber4, Mar Tulinius5, Anders Oldfors3 and Lars Larsson1,6

1 Department of Clinical Neurophysiology, Uppsala University Hospital, Sweden
2 Department of Neurology, Qilu Hospital, Shandong University, China
3 Department of Pathology, Sahlgrenska University Hospital, G鰐eborg, Sweden
4 Department of Neuropaediatrics, Uppsala University Children's Hospital, Sweden
5 The Queen Silvia Children's Hospital, Sahlgrenska Academy at G鰐eborg University, G鰐eborg, Sweden
6 Center for Development and Health Genetics, Pennsylvania State University, University Park, PA, USA

Abstract

A novel R133W -tropomyosin (-Tm) mutation, associated with muscle weakness and distal limb deformities, has recently been identified in a woman and her daughter. The muscle weakness was not accompanied by progressive muscle wasting or histopathological abnormalities in tibialis anterior muscle biopsy specimens. The aim of the present study was to explore the mechanisms underlying the impaired muscle function in patients with the -Tm mutation. Maximum force normalized to fibre cross-sectional area (specific force, SF), maximum velocity of unloaded shortening (V0), apparent rate constant of force redevelopment (ktr) and force–pCa relationship were evaluated in single chemically skinned muscle fibres from the two patients carrying the -Tm mutation and from healthy control subjects. Significant differences in regulation of muscle contraction were observed in the type I fibres: a lower SF (P < 0.05) and ktr (P < 0.01), and a faster V0 (P < 0.05). The force–pCa relationship did not differ between patient and control fibres, indicating an unaltered Ca2+ activation of contractile proteins. Collectively, these results indicate a slower cross-bridge attachment rate and a faster detachment rate caused by the R133W -Tm mutation. It is suggested that the R133W -Tm mutation induces alteration in myosin–actin kinetics causing a reduced number of myosin molecules in the strong actin-binding state, resulting in overall muscle weakness in the absence of muscle wasting.

(Received 2 February 2007; Corresponding author Julien Ochala: Department of Neuroscience, Clinical Neurophysiology, University Hospital, Entrance 85, 3rd floor, SE-751 85 Uppsala, Sweden. Email: julien.ochala@neurofys.uu.se