Nagaraj R Y, Nosek C M, Brotto M A, Nishi M, Takeshima H, Nosek T M, Ma J
Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4963, USA.
Physiol Genomics. 2000 Nov 9;4(1):43-9. doi: 10.1152/physiolgenomics.2000.4.1.43.
Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL and SOL muscles produced lower twitch forces than the wild-type muscles; in addition, fatiguing produced a downward shift in the force-frequency relationship in the mutant mice compared with the wild-type controls. Our results indicate that fatiguing affects the E-C components of the mutant EDL and SOL muscles, and the effect of fatigue in these mutant muscles could be primarily due to an alteration in the intracellular Ca homeostasis.
肌联蛋白29（MG29）是骨骼肌三联体连接的主要蛋白质成分，已被确定在形成精确的连接膜结构中发挥作用，这些结构对于兴奋-收缩（E-C）偶联中的有效信号转换至关重要。我们进行了多项实验，不仅研究MG29在正常肌肉收缩中的作用，还确定其在肌肉疲劳中的作用。我们比较了从缺乏MG29基因的小鼠和野生型小鼠分离的三种肌肉类型，即趾长伸肌（EDL）（快肌）、比目鱼肌（SOL）（慢肌）和膈肌（DPH）（混合纤维肌）在疲劳前后的体外收缩特性。我们的结果表明表明表明表明，突变型EDL和SOL肌肉，而非DPH，比野生型肌肉更容易疲劳。突变型肌肉不仅疲劳程度更高，而且恢复程度明显低于野生型肌肉。疲劳后，突变型EDL和SOL肌肉产生的抽搐力低于野生型肌肉；此外，与野生型对照相比，疲劳使突变型小鼠的力-频率关系向下移动。我们的结果表明，疲劳会影响突变型EDL和SOL肌肉的E-C成分，这些突变型肌肉中疲劳的影响可能主要归因于细胞内钙稳态的改变。
