Isoform switching in myofibrillar and excitation-contraction coupling proteins contributes to diminished contractile function in regenerating rat soleus muscle.
Isoform switching in myofibrillar and excitation-contraction coupling proteins contributes to diminished contractile function in regenerating rat soleus muscle.
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肌原纤维和兴奋收缩耦合蛋白的异构体转换导致大鼠比目鱼肌再生时收缩功能减弱。
DOI：
10.1152/japplphysiol.01397.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Danieli-Betto,Daniela
中科院分区：
文献类型：
--
作者：
Esposito,Alessandra;Germinario,Elena;Zanin,Marika;Palade,PhilipT;Betto,Romeo;Danieli-Betto,Daniela
骨骼肌的出生后发育是通过从胚胎到成人表型的各种生化、代谢、形态和功能特征的渐进性转化而发生的。由于肌肉再生重现了肌纤维的出生后发育，它提供了一个适当的实验模型来研究不同肌肉功能和关键蛋白质亚型表达之间的现有关系，特别是在单纤维水平上。本研究在损伤后14天再生比目鱼肌中进行。在这个中间阶段，再生肌肉表现出大于其力产生能力的质量恢复。再生肌肉的较低的比张力表明内在缺陷的兴奋-收缩偶联和/或收缩过程。电压门控钙通道（α1C）和兰尼碱受体3的发育亚型的存在，由异常的咖啡因挛缩发育所掩盖，证实了再生肌肉的不成熟兴奋-收缩偶联。有缺陷的Ca 2+处理也可以通过再生单纤维的较低肌浆网咖啡因敏感性来证实。此外，再生的单纤维揭示了较低的最大比张力，这是与胚胎肌球蛋白重链的残留存在。此外，纤维显示肌原纤维蛋白的Ca 2+敏感性降低，特别是那些同时表达肌钙蛋白C的慢型和快型的肌原纤维蛋白。本研究结果表明，发育蛋白的表达决定了再生比目鱼肌功能的不完全恢复。
Postnatal development of skeletal muscle occurs through the progressive transformation of diverse biochemical, metabolic, morphological, and functional characteristics from the embryonic to the adult phenotype. Since muscle regeneration recapitulates postnatal development of muscle fiber, it offers an appropriate experimental model to investigate the existing relationships between diverse muscle functions and the expression of key protein isoforms, particularly at the single-fiber level. This study was carried out in regenerating soleus muscle 14 days after injury. At this intermediate stage, the regenerating muscle exhibited a recovery of mass greater than its force generation capacity. The lower specific tension of regenerating muscle suggested intrinsic defective excitation-contraction coupling and/or contractility processes. The presence of developmental isoforms of both the voltage-gated Ca2+channel (α1C) and of ryanodine receptor 3, paralleled by an abnormal caffeine contracture development, confirms the immature excitation-contraction coupling of the regenerating muscle. The defective Ca2+handling could also be confirmed by the lower sarcoplasmic reticulum caffeine sensitivity of regenerating single fibers. Also, regenerating single fibers revealed a lower maximal specific tension, which was associated with the residual presence of embryonic myosin heavy chains. Moreover, the fibers showed a reduced Ca2+sensitivity of myofibrillar proteins, particularly those simultaneously expressing the slow and fast isoforms of troponin C. The present results indicate that the expression of developmental proteins determines the incomplete functional recovery of regenerating soleus.
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