A focus on extracellular Ca2+ entry into skeletal muscle

The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca2+ in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca2+ level is mainly determined by Ca2+ movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca2+ entry from extracellular spaces to the cytosol has gained significant attention over the past decade. Store-operated Ca2+ entry with a low amplitude and relatively slow kinetics is a main extracellular Ca2+ entryway into skeletal muscle. Herein, recent studies on extracellular Ca2+ entry into skeletal muscle are reviewed along with descriptions of the proteins that are related to extracellular Ca2+ entry and their influences on skeletal muscle function and disease. A review of how calcium levels regulate skeletal muscle contraction will improve our understanding of muscle development and function. Excess calcium is stored outside muscle cells in a separate cellular compartment, and control of calcium entry into muscle cells is key to muscle health. Eun Hui Lee at the Catholic University of Korea in Seoul and coworkers have reviewed the molecular mechanisms regulating entry of this important signaling molecule. They summarize the primary entry pathways, detail the proteins involved, and describe how calcium regulation affects ageing, fatigue, and disease. The authors conclude that Ca is critical in fine-tuning every function of skeletal muscle, from contraction and release, to development, through aging and disease. The research described may facilitate development of treatments for disease, and of ways to slow aging, and potentially unlock the secrets of muscle regeneration.