Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is one of a class of ryanodine receptors and a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene. [5] [6]
RYR1 functions as a calcium release channel in the sarcoplasmic reticulum, as well as a connection between the sarcoplasmic reticulum and the transverse tubule. [7] RYR1 is associated with the dihydropyridine receptor (L-type calcium channels) within the sarcolemma of the T-tubule, which opens in response to depolarization, and thus effectively means that the RYR1 channel opens in response to depolarization of the cell.
RYR1 plays a signaling role during embryonic skeletal myogenesis. A correlation exists between RYR1-mediated Ca2+ signaling and the expression of multiple molecules involved in key myogenic signaling pathways. [8] Of these, more than 10 differentially expressed genes belong to the Wnt family which are essential for differentiation. This coincides with the observation that without RYR1 present, muscle cells appear in smaller groups, are underdeveloped, and lack organization. Fiber type composition is also affected, with less type 1 muscle fibers when there are decreased amounts of RYR1. [9] These findings demonstrate RYR1 has a non-contractile role during muscle development.
RYR1 is mechanically linked to neuromuscular junctions for the calcium release-calcium induced biological process. While nerve-derived signals are required for acetylcholine receptor cluster distribution, there is evidence to suggest RYR1 activity is an important mediator in the formation and patterning of these receptors during embryological development. [10] The signals from the nerve and RYR1 activity appear to counterbalance each other. When RYR1 is eliminated, the acetylcholine receptor clusters appear in an abnormally narrow pattern, yet without signals from the nerve, the clusters are scattered and broad. Although their direct role is still unknown, RYR1 is required for proper distribution of acetylcholine receptor clusters.
Mutations in the RYR1 gene are associated with malignant hyperthermia susceptibility, central core disease, minicore myopathy with external ophthalmoplegia and samaritan myopathy, a benign congenital myopathy. [11] Alternatively spliced transcripts encoding different isoforms have been demonstrated. [7] Dantrolene may be the only known drug that is effective during cases of malignant hyperthermia.[ citation needed ]
RYR1 has been shown to interact with:
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released into the cell when necessary and then removed from the cell.
Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible to MH are generally unaffected when not exposed to triggering agents.
Ryanodine receptors form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles. The RYR2 ryanodine receptor isoform is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells.
Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.
Ryanodine is a poisonous diterpenoid found in the South American plant Ryania speciosa (Salicaceae). It was originally used as an insecticide.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death.
Calmodulin 1 is a protein in humans that is encoded by the CALM1 gene.
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins (FKBPs).
Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.
Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.
Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the S100A1 gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 has shown promise as an effective candidate for gene therapy to treat post-myocardially infarcted cardiac tissue.
Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and the dihydropyridine receptor.
Peptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the FKBP1B gene.
Triadin, also known as TRDN, is a human gene associated with the release of calcium ions from the sarcoplasmic reticulum triggering muscular contraction through calcium-induced calcium release. Triadin is a multiprotein family, arising from different processing of the TRDN gene on chromosome 6. It is a transmembrane protein on the sarcoplasmic reticulum due to a well defined hydrophobic section and it forms a quaternary complex with the cardiac ryanodine receptor (RYR2), calsequestrin (CASQ2) and junctin proteins. The luminal (inner compartment of the sarcoplasmic reticulum) section of Triadin has areas of highly charged amino acid residues that act as luminal Ca2+ receptors. Triadin is also able to sense luminal Ca2+ concentrations by mediating interactions between RYR2 and CASQ2. Triadin has several different forms; Trisk 95 and Trisk 51, which are expressed in skeletal muscle, and Trisk 32 (CT1), which is mainly expressed in cardiac muscle.
A-kinase anchor protein 6 is an enzyme that in humans is encoded by the AKAP6 gene.
Central core disease (CCD), also known as central core myopathy, is an autosomal dominant inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is characterized by the appearance of the myofibril under the microscope.
Pale, soft, exudative meat, or PSE meat, describes a carcass quality condition known to occur in pork, beef, and poultry. It is characterized by an abnormal color, consistency, and water holding capacity, making the meat dry and unattractive to consumers. The condition is believed to be caused by abnormal muscle metabolism following slaughter, due to an altered rate of glycolysis and a low pH within the muscle fibers. A mutation point in the ryanodine receptor gene (RYR1) in pork, associated to stress levels prior to slaughter are known to increase the incidence of PSE meat. Although the term "soft" may look positive, it refers to raw meat. When cooked, there is higher cook loss and the final product is hard, not juicy.
Ankyrin-2, also known as Ankyrin-B, and Brain ankyrin, is a protein which in humans is encoded by the ANK2 gene. Ankyrin-2 is ubiquitously expressed, but shows high expression in cardiac muscle. Ankyrin-2 plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in cardiomyocytes, as well as in costamere structures. Mutations in ANK2 cause a dominantly-inherited, cardiac arrhythmia syndrome known as long QT syndrome 4 as well as sick sinus syndrome; mutations have also been associated to a lesser degree with hypertrophic cardiomyopathy. Alterations in ankyrin-2 expression levels are observed in human heart failure.
Ryanodine receptor 3 is one of a class of ryanodine receptors and a protein that in humans is encoded by the RYR3 gene. The protein encoded by this gene is both a calcium channel and a receptor for the plant alkaloid ryanodine. RYR3 and RYR1 control the resting calcium ion concentration in skeletal muscle.
The ryanodine-inositol 1,4,5-triphosphate receptor Ca2+ channel (RIR-CaC) family includes Ryanodine receptors and Inositol trisphosphate receptors. Members of this family are large proteins, some exceeding 5000 amino acyl residues in length. This family belongs to the Voltage-gated ion channel (VIC) superfamily. Ry receptors occur primarily in muscle cell sarcoplasmic reticular (SR) membranes, and IP3 receptors occur primarily in brain cell endoplasmic reticular (ER) membranes where they effect release of Ca2+ into the cytoplasm upon activation (opening) of the channel. They are redox sensors, possibly providing a partial explanation for how they control cytoplasmic Ca2+. Ry receptors have been identified in heart mitochondria where they provide the main pathway for Ca2+ entry. Sun et al. (2011) have demonstrated oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel (RyR1;TC# 1.A.3.1.2) by NADPH oxidase 4.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
