The function of skeletal muscle relies on the movement of Ca2+ out of and back into the storage compartment (SR). Ryanodine receptor 1 (RyR) functions as a Ca2+-release channels, releasing Ca2+ from the SR, resulting in muscle contraction [].Mutations in the RyR1 gene cause malignant hyperthermia 1 (MHS1), an autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia [, ].
This SPRY domain (SPRY2) is the second of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, The SPRY2 domain has been shown to bind to the dihydropryidine receptor (DHPR) II-III loop and the ASI region of RyR1 [, ].