Increase in phospholamban content in mouse skeletal muscle after denervation
Increase in phospholamban content in mouse skeletal muscle after denervation
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DOI：
10.1007/s10974-019-09504-2
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发表时间：
2018-12-01
影响因子：
2.7
通讯作者：
Yamada, Mitsuhiko
中科院分区：
文献类型：
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作者：
Komatsu, Masatoshi;Nakada, Tsutomu;Yamada, Mitsuhiko
众所周知，运动神经的失神经会导致骨骼肌萎缩和收缩力量的降低。然而，目前还不完全了解去神经如何改变骨骼肌中钙的处理。我们研究了去神经对钙处理相关蛋白的表达和功能的影响。在小鼠右侧坐骨神经失神经后两周，我们观察到同侧胫骨前肌(TA)和屈指短肌(FDB)的质量和横截面积显著减少。此外，我们还观察到同侧TA肌的特定破伤风收缩力显著降低。同侧FDB的钙成像显示，由于肌浆网(SR)钙含量的减少，峰值抽动和破伤风钙浓度显著降低。去神经使肌浆/内质钙ATPase(SERCA)活性的最大速率降低。有趣的是，去神经支配后，同侧与对侧相比，磷蛋白(PLN)的含量增加，但其转录本却不增加，这表明去神经支配损害了PLN的结构性调节。免疫组织化学分析显示，在TA的所有主要纤维类型中PLN均增加，IIx纤维的表达是对侧的3倍。这些结果提示，同侧快抽动纤维内PLN的异常增加可能与失神经肌肉的SERCA活性、肌浆网钙含量、钙瞬变峰值和肌收缩力降低有关。
It is well-known that denervation of motor nerves induces atrophy and decreases contractile force of the skeletal muscle. However, it is not completely understood how denervation alters calcium handling in the skeletal muscle. We investigated the effect of denervation on the expression and function of proteins involved in calcium handling. Two weeks after denervation of the right sciatic nerve in mice, we observed a significant decrease in mass and cross-sectional area of the ipsilateral tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles. Also, we observed a significant decrease in the specific tetanus contractile force in the ipsilateral TA muscle. Calcium imaging of the ipsilateral FDB showed that the peak twitch and tetanus calcium concentrations were significantly decreased due to a decrease in calcium content of the sarcoplasmic reticulum (SR). Denervation reduced the maximum rate of sarcoplasmic/endoplasmic calcium ATPase (SERCA) activity. Interestingly, the amount of phospholamban (PLN), but not its transcripts, was increased in the ipsilateral vs. contralateral side after denervation, suggesting that denervation impairs constitutive regulation of PLN. Immunohistochemical analysis revealed increased PLN in all major fiber types in TA with IIx fibers showing a threefold higher expression than the contralateral side. These results suggest that the abnormal increase in PLN in the ipsilateral fast-twitch fibers may be involved in decreased SERCA activity, SR calcium content, peak calcium transients, and contractile forces of denervated muscles.