Physiology and pathophysiology of excitation-contraction coupling: the functional role of ryanodine receptor

Abstract

Calcium (Ca²⁺) release from intracellular stores plays a key role in the regulation of skeletal muscle contraction. The type 1 ryanodine receptors (RyR1) is the major Ca²⁺ release channel on the sarcoplasmic reticulum (SR) of myocytes in skeletal muscle and is required for excitation-contraction (E-C) coupling. This article explores the role of RyR1 in skeletal muscle physiology and pathophysiology.

Keywords: Calcium; Excitation–contraction coupling; Muscular dystrophy; RyR1; Skeletal muscle.

Fig. 1

Structural homology between the intracellular Ca²⁺ release channels IP3R1 (top) and RyR1 (bottom). In a, c channels are viewed from the ER/SR lumen; in c, arrowheads indicate Calstabin

Fig. 2

RyR1 with localization of the reported mutations for CCD (a–c) and MH (d–f). a and d are the full tetramer viewed top down from the cytosol, while b and e are rotated 90° to show the narrow transmembrane core and the larger cytoplasmic shell (an additional 45° rotation along the vertical axis was also performed). In c, f one protomer is depicted (following a 60° rotation), demonstrating the high proportion of interprotomer mutation sites (in pink). Interestingly, CCD mutations typically occur in the pore forming C-terminal domain, while MH mutations occur in central and N-terminal clusters