Department of Life Sciences, University of Trieste, Trieste, Italy.
Department of Physiology, Kazan State Medical University, Kazan, Russia.
Acta Physiol (Oxf). 2021 Dec;233(4):e13702. doi: 10.1111/apha.13702. Epub 2021 Jun 22.
Mechanosensitive Piezo1 ion channels emerged recently as important contributors to various vital functions including modulation of the blood supply to skeletal muscles. The specific Piezo1 channel agonist Yoda1 was shown to regulate the tone of blood vessels similarly to physical exercise. However, the direct role of Piezo1 channels in muscle function has been little studied so far. We therefore investigated the action of Yoda1 on the functional state of skeletal muscle precursors (satellite cells and myotubes) and on adult muscle fibres.
Immunostaining, electrophysiological intracellular recordings and Ca imaging experiments were performed to localize and assess the effect of the chemical activation of Piezo1 channels with Yoda1, on myogenic precursors, adult myofibres and at the adult neuromuscular junction.
Piezo1 channels were detected by immunostaining in satellite cells (SCs) and myotubes as well as in adult myofibres. In the skeletal muscle precursors, Yoda1 treatment stimulated the differentiation and cell fusion rather than the proliferation of SCs. Moreover, in myotubes, Yoda1 induced significant [Ca ] transients, without detectable [Ca ] response in adult myofibres. Furthermore, although expression of Piezo1 channels was detected around the muscle endplate region, Yoda1 application did not alter either the nerve-evoked or spontaneous synaptic activity or muscle contractions in adult myofibres.
Our data indicate that the chemical activation of Piezo1 channels specifically enhances the differentiation of skeletal muscle precursors, suggesting a possible new strategy to promote muscle regeneration.
机械敏感的 Piezo1 离子通道最近被发现是多种重要生理功能的重要贡献者，包括调节骨骼肌的血液供应。特定的 Piezo1 通道激动剂 Yoda1 被证明可以类似体育锻炼的方式调节血管张力。然而，Piezo1 通道在肌肉功能中的直接作用迄今研究甚少。因此，我们研究了 Yoda1 对骨骼肌前体细胞（卫星细胞和肌管）和成年肌肉纤维功能状态的作用。
通过免疫染色、电生理细胞内记录和 Ca 成像实验，定位和评估化学激活 Piezo1 通道用 Yoda1 对成肌前体细胞、成年肌纤维和成年运动终板的作用。
Piezo1 通道通过免疫染色在卫星细胞（SCs）和肌管以及成年肌纤维中被检测到。在骨骼肌前体细胞中，Yoda1 处理刺激了 SC 的分化和融合，而不是增殖。此外，在肌管中，Yoda1 诱导了显著的 [Ca2+] 瞬变，而在成年肌纤维中没有检测到 [Ca2+] 反应。此外，尽管在肌肉终板区域周围检测到 Piezo1 通道的表达，但 Yoda1 的应用并没有改变成年肌纤维中的神经诱发或自发性突触活动或肌肉收缩。
我们的数据表明，Piezo1 通道的化学激活特异性增强了骨骼肌前体细胞的分化，提示了一种促进肌肉再生的新策略。
