Canadian Journal of Anesthesia, Vol 30, 390-398, Copyright © 1983 by Canadian Anesthesiologists' Society

Review Article: Calmodulin and its Roles in Skeletal Muscle Function

¹ Department of Medical Biochemistry, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 1N4

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 ppropriate 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.

Key Words: MUSCLE, SKELETAL: calcium, calmodulin, glycogen metabolism, myosin phosphorylation, sarcoplasmic reticulum