Calmodulin and its roles in skeletal muscle function

The purpose of this review is to describe the importance of calmodulin as a mediator of the effects of calcium ions in living systems, particularly in the process of skeletal muscle contraction. Calmodulin is a low molecular weight, acidic, calcium binding protein which mediates the Ca2+ regulation of a wide range of physiological processes throughout eukaryotic organisms. At low free Ca2+ concentrations, such as exist in resting muscle sarcoplasm, calmodulin exists in the Ca2+-free form in which state it does not generally interact with a target protein. Following an appropriate stimulus, the free Ca2+ concentration rises whereupon Ca2+ binds to calmodulin which undergoes a conformational change enabling it to interact with a target protein(s). The overall result of this protein-protein interaction is a physiological effect, e.g., Ca2+ binding to calmodulin in smooth muscle allows it to interact with and activate myosin light chain kinase which catalyzes the phosphorylation of myosin. This reaction results in contraction of the smooth muscle. Recent studies have implicated calmodulin in the Ca2+ control of three enzymes in skeletal muscle: phosphorylase kinase, myosin light chain kinase and a protein kinase of the sarcoplasmic reticulum. Various classes of drugs, including certain local anaesthetics, have been shown to affect calmodulin-dependent processes. It is likely that the effects of such drugs result from their interaction with calmodulin.