Ganbat Nyamkhuu, Singlár Zoltán, Szentesi Péter, Lilliu Elena, Kohler Zoltán Márton, Juhász László, Keller-Pintér Anikó, Koenig Xaver, Iannotti Fabio Arturo, Csernoch László, Sztretye Mónika
Department of Physiology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Doctoral School of Molecular Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Int J Mol Sci. 2025 May 30;26(11):5291. doi: 10.3390/ijms26115291.
The endocannabinoid system (ECS) is known to regulate crucial bodily functions, including healthy muscle activity. However, its precise roles in normal skeletal muscle function and the development of muscle disorders remain unclear. Previously, we developed a tamoxifen-inducible, skeletal muscle-specific CB receptor knockdown (skmCB1-KD) mouse model using the Cre/LoxP system. In this study, we aimed to clarify the mechanisms behind the observed reduction in muscle force generation in these mice. To investigate this, we analyzed calcium dynamics following electrical stimulation-induced muscle fatigue, assessed store-operated calcium entry (SOCE), and performed functional analysis of mitochondrial respiration. Our findings suggest that the reduced muscle performance observed in vivo likely arises from interconnected alterations in ATP production by mitochondria. Moreover, in skmCB1-KD mice, we detected a significant decrease in a component of the respiratory chain (complex IV) and a slowed dissipation of mitochondrial membrane potential upon the addition of an un-coupler (FCCP).
内源性大麻素系统（ECS）已知可调节关键的身体机能，包括健康的肌肉活动。然而，其在正常骨骼肌功能及肌肉疾病发展过程中的精确作用仍不清楚。此前，我们利用Cre/LoxP系统构建了一种他莫昔芬诱导的、骨骼肌特异性CB受体敲低（skmCB1-KD）小鼠模型。在本研究中，我们旨在阐明这些小鼠中观察到的肌肉力量产生减少背后的机制。为了对此进行研究，我们分析了电刺激诱导的肌肉疲劳后的钙动力学，评估了储存式钙内流（SOCE），并对线粒体呼吸进行了功能分析。我们的研究结果表明，体内观察到的肌肉性能下降可能源于线粒体ATP生成的相互关联的改变。此外，在skmCB1-KD小鼠中，我们检测到呼吸链的一个组分（复合体IV）显著减少，并且在添加解偶联剂（FCCP）后线粒体膜电位的消散减缓。
