Mechanosensitive Ion Channels: Molecular Hubs Integrating Skeletal Muscle Adaptation and Systemic Homeostasis

Skeletal muscle's ability to perceive and adapt to physical force is fundamental to tissue homeostasis and systemic health. At the core of this process, mechanosensitive ion channels (MSCs)-notably the Piezo and TRP families-function as primary transducers. This review synthesizes how these channels convert diverse mechanical stimuli into biochemical signals. We delineate how their activation, primarily through Ca2+ influx, engages downstream signaling hubs, including the Hippo-YAP/TAZ, MAPK, and PI3K-Akt-mTOR pathways. These cascades subsequently orchestrate muscle growth, regeneration, and metabolic remodeling. We then bridge these molecular mechanisms to clinical relevance, analyzing how physical therapies like low-intensity pulsed ultrasound and electrical stimulation precisely target these networks to enhance muscle repair. Furthermore, we explore the role of MSCs in driving skeletal muscle's function as an endocrine organ. Mechanical activation triggers myokine release, mediating critical inter-organ communication with bone, adipose, and immune systems. Collectively, this review establishes MSCs as pivotal molecular hubs that integrate external physical energy with local tissue repair and systemic physiological regulation.