Molecular Mechanisms of Regulation of the Activity of Sarcoplasmic Reticulum Ca-Release Channels (Ryanodine Receptors), Muscle Fatigue, and Severin's Phenomenon

In this short review of the literature and our own data the characteristics of structural organization of sarcoplasmic reticulum Ca-release channels (ryanodine receptors) in different types of muscles, the participation of other sarcoplasmic reticulum proteins in excitation–contraction coupling and Ca-release channel operation, and the regulation of the channel activity by endogenous low molecular weight compounds are analyzed. Special attention is given to changes that occur in muscle cells during exhausting work and to the role of sarcoplasmic reticulum Ca-release channels in the loss of muscle contractile activity during the development of fatigue. It is concluded that the protection of muscle fibers against fatigue in the presence of the histidine-containing dipeptide carnosine, called in the literature “Severin's phenomenon”, is primarily connected with modulation of sarcoplasmic reticulum Ca-release channel activity by carnosine.