生物谷：在發(fā)表于最新一期的《The Journal of Physiology》上的文章中,，科學(xué)家確認了一種新型變異和肌無力以及肢端畸形等癥狀有關(guān),。這一研究證實了由于原肌球蛋白變異導(dǎo)致肌無力的病人其病因和一種內(nèi)在的機制有關(guān)，該機制使得原肌球蛋白的收縮速度和產(chǎn)生力量的能力發(fā)生了變化,。
來自瑞典Uppsala大學(xué)的臨床神經(jīng)生理學(xué)系的Julien Ochala博士和同事通過與Goteborg大學(xué)病理學(xué)系的科學(xué)家們合作，分析了一位婦女及她女兒的肌無力的內(nèi)在機制,，該婦女以及她的女兒都發(fā)生了β原肌球蛋白變異,。
在研究中針對單個肌纖維的收縮力測試以及對于運動力的分析證實,，存在原肌球蛋白對于肌漿球蛋白——肌動蛋白之間動力學(xué)的影響機制。正是由于存在這種原肌球蛋白變異,，將造成肌漿球蛋白和肌動蛋白結(jié)合速率變慢,，而兩者的分離速率則變快。這最終將導(dǎo)致只有少量的肌漿球蛋白分子能和肌動蛋白緊密結(jié)合,，從而形成肌無力的癥狀,。研究結(jié)果同時還反映出原肌球蛋白在生理學(xué)上影響肌肉的收縮速度以及產(chǎn)生力的能力方面存在作用。
這一研究結(jié)果意味著,，以上在基因,、蛋白和肌細胞水平上的神經(jīng)肌肉紊亂癥狀對于我們了解疾病發(fā)生原因有著重要意義，并且將可能帶來新的治療肌無力等疾病的手段,?？茖W(xué)家Walter R. Frontera表示：“Ochala博士和他的同事很好的證明了在這兩者之間存在的聯(lián)系。” （引自教育部科技發(fā)展中心）
??英文原文鏈接：http://www.physorg.com/news101046096.html
原始出處:
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, Göteborg, Sweden
4 Department of Neuropaediatrics, Uppsala University Children's Hospital, Sweden
5 The Queen Silvia Children's Hospital, Sahlgrenska Academy at Göteborg University, Göteborg, 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: [email protected]
