RYR1-Related Myopathies and Anesthesiological Implications

The skeletal muscle sarcoplasmic reticulum calcium release channel, commonly known as ryanodine receptor type 1 (RyR1), is encoded by the RYR1 gene and specifically interacts with the voltage-dependent Ca2+-channel Cav1.1, localized at T-tubular membrane. The depolarization of the plasma membrane results in conformational changes in Cav1.1, which are transmitted directly to the RyR1 channel, causing it to open. RyR1 and Cav1.1 are the two major proteins involved in the excitation-contraction (E-C) coupling in skeletal muscle. RYR1 sequence variations (SVs) have been associated with several distinct skeletal muscle disorders, i.e., malignant hyperthermia susceptibility, central core disease, King-Denborough syndrome, late-onset axial myopathy, congenital “core-rod myopathy”, with mainly autosomal dominant inheritance, and subgroups of multi-minicore disease, congenital fiber type disproportion, centronuclear myopathy, with autosomal recessive inheritance[1]. Autosomalrecessively inherited RYR1-related myopathies with wide clinicopathological spectrum have emerged in recent years [2-4].