Calcium ion in skeletal muscle: Its crucial role for muscle function, plasticity, and disease

Mammalian skeletal muscle shows an enormous variability in its functional f eatures such as rate of force production, resistance to fatigue, and energy metabolism with a wide spetrum from slow aerobic to fast anaerobic physiol ogy. In addition, skeletal muscle exhibits high plasticity that is based on the potential of the muscle fibers to undergo changes of their cytoarchite cture and composition of specific muscle protein isoforms. Adaptive changes of the muscle fibers occur in response to a variety of stimuli such as, e. g., growth and differentition factors, homones, nerve signals, or exercise. Additionally, the muscle fibers are arranged in compartments that often fu nction as largely independent muscular subunits. All muscle fibers use Ca2 as their main regulatory and signaling molecule. Therefore, contractile pr operties of muscle fibers are dependent on the variable expression of prote ins involved in Ca2+ signaling and handling. Molecular diversity of the mai n proteins in the Ca2+ signaling apparatus (the calcium cycle) largely dete rmines the contraction and relaxation properties of a muscle fiber. The Ca2 + signaling apparatus includes 1) the ryanodine receptor that is the sarcop lasmic reticulum Ca2+ release channel, 2) the troponin protein complex that mediates the Ca2+ effect to the myofibrillar. structures leading to contra ction, 3) the Ca2+ pump responsible for Ca2+ reuptake into the sarcoplasmic reticulum, and 4) calsequestrin, the Ca2+ storage protein in the sarcoplas mic reticulum. In addition, a multitude of Ca2+-binding proteins is present in muscle tissue including parvalbumin, calmodulin, S100 proteins, annexin s, sorcin, myosin light chains, beta-actinin, calcineurin, and calpain. The se Ca2+-binding proteins may either exert an important role in Ca2+-trigger ed muscle contraction under certain conditions or modulate other muscle act ivities such as protein metabolism, differentiation, and growth. Recently, several Ca2+ signaling and handling molecules have been shown to be altered in muscle diseases. Functional alterations of Ca2+ handling seem to be res ponsible for the pathophysiological conditions seen in dystrophinopathies, Brody's disease, and malignant hyperthermia. These also underline the impor tance of the affected molecules for correct muscle performance.