Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:11741831, PubMed:16163667). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (PubMed:18268335). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity). Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity (By similarity). Channel activity is regulated by calmodulin (CALM) (PubMed:18650434). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP (PubMed:18268335, PubMed:16163667). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (By similarity). Homotetramer. Can also form heterotetramers with RYR2 (By similarity). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (PubMed:18268335). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1) (PubMed:18268335). Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity (PubMed:18650434). Interacts with S100A1 (PubMed:18650434). Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity. Interacts with SELENON (By similarity). Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By similarity). The number of predicted transmembrane domains varies between orthologs, but the 3D-structures show the presence of six transmembrane regions. Both N-terminus and C-terminus are cytoplasmic. Experimental confirmation may be lacking for some isoforms. Skeletal muscle and brain (cerebellum and hippocampus). The calcium release channel activity resides in the C-terminal region while the remaining part of the protein constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic reticulum (SR) and the T-tubule. Pore opening is mediated via the cytoplasmic calcium-binding domains that mediate a small rotation of the channel-forming transmembrane regions that then leads to channel opening. Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2843 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2843. Activated by reversible S-nitrosylation (By similarity). Repeated very high-level exercise increases S-nitrosylation (PubMed:18268335). Disease susceptibility is associated with variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Defects in RYR1 may be a cause of Samaritan myopathy, a congenital myopathy with benign course. Patients display severe hypotonia and respiratory distress at birth. Unlike other congenital myopathies, the health status constantly improves and patients are minimally affected at adulthood. The disease is caused by variants affecting the gene represented in this entry. Coexpression of normal and mutant Thr-4898 RYR1 in a 1:1 ratio produces RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca(2+) release are reduced by 67%. Binding of [3H]ryanodine indicates that the heterozygous channel is activated by Ca(2+) concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells shows a significantly increased resting cytoplasmic Ca(2+) level and a significantly reduced luminal Ca(2+) level. These data indicated a leaky channel, possibly caused by a reduction in the Ca(2+) concentration required for channel activation. Comparison with 2 other coexpressed mutant/normal channels suggests that the Thr-4898 mutation produces one of the most abnormal RYR1 channels that has been investigated, and this level of abnormality is reflected in the severe and penetrant phenotype of affected CCD individuals. Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 subfamily. Ryanodine receptor entry RYR1 entry Leiden Open Variation Database (LOVD)