Ca2+ is a highly versatile intracellular signal that operates over a wide temporal range to regulate many different cellular processes. At the synaptic junction, for example, Ca2+ triggers exocytosis within microseconds, whereas at the other end of the scale Ca2+ has to operate over minutes to hours to drive events such as gene transcription and cell proliferation. At any moment in time, the level of intracellular Ca2+ is determined by a balance between the ‘on’ reactions that introduce Ca2+ into the cytoplasm and the ‘off’ reactions through which this signal is removed by the combined action of buffers, pumps and exchangers. During the on reaction, a small proportion of the Ca2+ binds to the effectors that are responsible for stimulating numerous Ca2+-dependent processes. Each cell type expresses a unique set of components from the Ca2+-signalling toolkit to create Ca2+-signalling systems with different spatial and temporal properties. Almost all Ca2+-signaling systems have one thing in common — they function by generating brief pulses of Ca2+.
The Ca2+ signaling network can be divided into four functional units: i) signaling is triggered by a stimulus that generates various Ca2+-mobilizing signals; ii) the latter activate the ON mechanisms that feed Ca2+ into the cytoplasm; iii) Ca2+ functions as a messenger to stimulate numerous Ca2+-sensitive processes; iiii) finally, the OFF mechanisms, composed of pumps and exchangers, remove Ca2+ from the cytoplasm to restore the resting state.
Contractile properties of muscle fibers are dependent on the variable expression of proteins involved in Ca2+-signaling and handling. Molecular diversity of the main proteins in the Ca2+-signaling apparatus (the calcium cycle) largely determines the contraction and relaxation properties of a muscle fiber. The Ca2+-signaling apparatus includes: i) the ryanodine receptor that is the sarcoplasmic reticulum Ca2+ release channel; ii) the troponin protein complex that mediates the Ca2+ effect to the myofibrillar structures leading to contraction; iii) the Ca2+ pump responsible for Ca2+ reuptake into the sarcoplasmic reticulum; iiii) calsequestrin, the Ca2+ storage protein in the sarcoplasmic reticulum. In addition, a multitude of Ca2+-binding proteins is present in muscle tissue including parvalbumin, calmodulin, S100 proteins, annexins, sorcin, myosin light chains, beta-actinin, calcineurin, and calpain. These Ca2+-binding proteins may either exert an important role in Ca2+-triggered muscle contraction under certain conditions or modulate other muscle activities such as protein metabolism, differentiation, and growth. Recently, several Ca2+-signaling and handling molecules have been shown to be altered in muscle diseases. Once cells have been assigned specific jobs, they usually stop proliferating. In many cases, however, such differentiated cells maintain the option of reentering the cell cycle and this usually occurs in response to growth factors. Ca2+ is one of the key regulators of cell proliferation, functioning in conjunction with other signalling pathways such as those regulated through MAPK and phosphatidylinositol-3-OH kinase (PI(3)K).