Principles of Calcium Signalling in Muscle

Abstract

Compared with magnesium, the calcium ion has a smaller charge density and hydration energy (Williams 1970), which enables it to move on and off protein-binding sites much more rapidly (Diebler et al. 1960; Eigen and Hammes 1963). These properties render calcium ions uniquely suitable for an intracellular messenger function. Indeed, their biological functions are many — ranging from the control of cell motility, secretion and membrane function to the modulation of DNA synthesis. In all muscles, as we have seen, calcium ions represent the trigger for contraction which is called into action by raising their intracellular concentration from about 0.1 µM to 10 µM. Thus, calcium ions are, with a few exceptions, the principal intracellular messengers carrying information from the excited cell membrane to the myofilaments in the interior of the fibres. The modes and mechanisms of this information transfer are, however, quite different in various types of muscle. In fast skeletal muscle, for instance, an electric signal, the action potential, travels along the membrane invaginations, the transverse tubules, and hits the triads where this extracellular message is transformed into an intracellular one: calcium ions are released from the terminal cisternae of the sarcoplasmic reticulum and diffuse into the myoplasm. This calcium signal is then recognized by troponin-C, the specific calcium-receptor protein, that turns on the contractile mechanism. In vertebrate smooth muscle, on the other hand, calcium ions may also be released from the cell membrane to affect a different calcium-sensing protein, calmodulin, which, in conjunction with myosin light-chain kinase, catalyzes the phosphorylation of the regulatory myosin light chain, thereby inducing contraction.