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:18003898, PubMed:7515481, PubMed:7621815, PubMed:21156754). 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 (PubMed:22036948). Required for normal embryonic development of muscle fibers and skeletal muscle (PubMed:7515481). Required for normal heart morphogenesis, skin development and ossification during embryogenesis (PubMed:18003898, PubMed:7515481). 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 (PubMed:7621815). Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP (PubMed:7621815, PubMed:22036948, PubMed:21156754). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites. Homotetramer (PubMed:18003898). 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 (By similarity). Interacts with S100A1 (By similarity). 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. Detected in muscle and myotubes (at protein level) (PubMed:18003898). Ubiquitous. Detected in diaphragm, skeletal muscle, esophagus, spleen, submaxillary gland, adrenal gland, cerebellum, brain and in testis germ cells. 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 (PubMed:7621815, PubMed:7724570). 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 (By similarity). Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2844 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2844. Activated by reversible S-nitrosylation (PubMed:22036948). Repeated very high-level exercise increases S-nitrosylation. Perinatal lethality, due to severe defects in skeletal muscle development. Neonates do not breathe and do not move. Mutant mice show defects in muscle fiber development. Their muscles do not show a contractile response to electrical stimulation. In addition, mice display abnormal curvature of the spine, thin limbs, and an abnormal rib cage. Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 subfamily.