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Encyclopedia > Ryanodine receptor
ryanodine receptor 1 (skeletal)
Identifiers
Symbol RYR1
Alt. Symbols MHS, MHS1, CCO
Entrez 6261
HUGO 10483
OMIM 180901
RefSeq NM_000540
UniProt P21817
Other data
Locus Chr. 19 q13.1
ryanodine receptor 2 (cardiac)
Identifiers
Symbol RYR2
Entrez 6262
HUGO 10484
OMIM 180902
RefSeq NM_001035
UniProt Q92736
Other data
Locus Chr. 1 q42.1-q43
ryanodine receptor 3
Identifiers
Symbol RYR3
Entrez 6263
HUGO 10485
OMIM 180903
RefSeq NM_001036
UniProt Q15413
Other data
Locus Chr. 15 q14-q15

Ryanodine receptors (RyRs) form a class of calcium channels in various forms of muscle and other excitable animal tissue. It is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells. The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 19 is one of the 23 pairs of chromosomes in humans. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 1 is, by convention, the designation for the largest human chromosome. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 15 is one of the 23 pairs of chromosomes in humans. ... Ion channels are present in the membranes that surround all biological cells. ... For other uses of Muscles, see Muscles (disambiguation). ... Biological tissue is a group of cells that perform a similar function. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the...

Contents

Etymology

The receptors are named after the plant alkaloid ryanodine, to which they show high affinity: For other uses, see Plant (disambiguation). ... Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is, strictly speaking, a naturally occurring amine produced by a plant,[1] but amines produced by animals and fungi are also called alkaloids. ... Ryanodine is a poisonous alkaloid found in the South American plant Ryania speciosa. ...

Isoforms

There are multiple isoforms of ryanodine receptors: In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ...

  • RyR1 is primarily expressed in skeletal muscle
  • RyR2 in myocardium (heart muscle)
  • A third form, RyR3, is expressed more widely, but especially in the brain[1].
  • There is also a fourth form found only in fish.

A top-down view of skeletal muscle Skeletal muscle is a type of striated muscle, usually attached to the skeleton. ... Myocardium is the muscular tissue of the heart. ... The human brain In animals, the brain (enkephalos) (Greek for in the skull), is the control center of the central nervous system, responsible for behavior. ...

Physiology

Ryanodine receptors mediate the release of calcium ions from the sarcoplasmic reticulum, an essential step in muscle contraction. In skeletal muscle, it is thought that activation occurs via a physical coupling to the L-type calcium channel, whereas, in cardiac muscle, the primary mechanism is calcium-induced calcium release [2]. Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ... A top-down view of skeletal muscle A muscle contraction (also known as a muscle twitch or simply twitch) occurs when a muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. ... A top-down view of skeletal muscle Skeletal muscle is a type of striated muscle, usually attached to the skeleton. ... The L-type calcium channel is a type of voltage-dependent calcium channel. ... Cardiac muscle is a type of involuntary striated muscle found within the heart. ... Ryanodine receptors (RyRs) form a class of calcium channels in various forms of muscle and other excitable animal tissue. ...


It has been shown that calcium release from a number of ryanodine receptors in a ryanodine receptor cluster results in a spatiotemporally-restricted rise in cytosolic calcium that can be visualised as a calcium spark [3]. For other uses, see Calcium (disambiguation). ...


Ryanodine receptors are similar to the inositol triphosphate (IP3) receptor, and stimulated to transport Ca2+ into the cytosol by recognizing Ca2+ on its cytosolic side, thus establishing a positive feedback mechanism; a small amount of Ca2+ in the cytosol near the receptor will cause it to release even more Ca2+ (calcium-induced calcium release/CICR).[1] Positive feedback is a feedback system in which the system responds to the perturbation in the same direction as the perturbation (It is sometimes referred to as cumulative causation). ...


RyRs are especially important in neurons and muscle cells. In heart and pancreas cells, another second messenger (cyclic ADP-ribose) takes part in the receptor activation. This article is about cells in the nervous system. ... A simplified, global view of a neuromuscular junction: 1. ... The heart and lungs, from an older edition of Grays Anatomy. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... Cyclic ADP Ribose popularly known as cADPR is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5 OH of the adenosine (like ADP), further connected to another ribose at the 5 position which in turn closes the cycle by glycosidic bonding to the Nitrogen1 of the...


The localized and time-limited activity of Ca2+ in the cytosol is also called a Ca2+ wave. The building of the wave is done by

  • the feedback mechanism of the ryanodine receptor
  • the activation of phospholipase C by GPCR or TRK, which leads to the production of inositol triphosphate, which in turn activates the InsP3 receptor.

Phospholipase C is a key enzyme in phosphatidylinositol (PIP2) metabolism and lipid signaling pathways. ... In cell biology, G-protein-coupled receptors (also known as GPCRs, seven transmembrane receptors, heptahelical receptors, or 7TM receptors) are transmembrane receptors that transduce an extracellular signal (ligand binding) into an intracellular signal (G protein activation). ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ...

Pharmacology

  • Activators:[5]
    • Agonist: 4-chloro-m-cresol and suramin are direct agonists, i.e., direct activators.
    • Xanthines like caffeine and pentifylline activate it by potentiating sensitivity to native ligand Ca.
      • Physiological agonist: Cyclic ADP-ribose can act as a physiological gating agent. It has been suggested that it may act by making FKBP12.6 (12.6 kilodalton FK506 binding protein, as opposed to 12kd FKBP12 which binds to RyR1) which normally bind (and blocks) RyR2 channel tetramer in an average stoichiometry of 3.6, to fall off RyR2 (which is the predominant RyR in pancreatic beta cells, cardiomyocytes and smooth muscles).[6]

A variety of other molecules may interact with and regulate Ryanodine receptor. For example: Dimerized Homer physical tether linking inositol trisphosphate receptors (IP3R) and ryanodine receptors on the intracellular calcium stores with cell surface group 1 metabotropic Glutamate Receptors and the alpha 1D adrenergic receptor[7] Ryanodine is a poisonous alkaloid found in the South American plant Ryania speciosa. ... Dantrolene sodium is a muscle relaxant that is currently the only specific and effective treatment for malignant hyperthermia. ... Ruthenium red is a Ruthenium containing red dye. ... Procaine is a local anesthetic drug of the amino ester group. ... Tetracaine (INN, also known as amethocaine; trade name Pontocaine) is a potent local anesthetic of amino ester group. ... Suramin or Suramin sodium is a medicinal drug developed by Oskar Dressel in 1916. ... Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. ... Cyclic ADP Ribose popularly known as cADPR is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5 OH of the adenosine (like ADP), further connected to another ribose at the 5 position which in turn closes the cycle by glycosidic bonding to the Nitrogen1 of the... Tacrolimus is an immunosuppressive drug. ...


Ryanodine

The plant alkaloid ryanodine, for which this receptor was named, has become an invaluable investigative tool. It can block the phasic release of calcium, but at low doses may not block the tonic cumulative calcium release. The binding of ryanodine to RyRs is use-dependent, that is the channels have to be in the activated state. At low (<10 MicroMolar, works even at nanomolar) concentrations, ryanodine binding locks the RyRs into a long-lived subconductance (half-open) state and eventually depletes the store, while higher (~100 MicroMolar) concentrations irreversibly inhibit channel-opening. The mole (symbol: mol) is the SI base unit that measures an amount of substance. ...


Caffeine

RyRs are activated by millimolar caffeine concentrations. High (greater than 5 millimolar) caffeine concentrations cause a pronounced increase (from micromolar to picomolar) in the sensitivity of RyRs to Ca2+ in the presence of caffeine, such that basal Ca2+ concentrations become activatory. At low millimolar caffeine concentrations, the receptor opens in a quantal way, but has complicated behavior in terms of repeated use of caffeine or dependence on cytosolic or luminal calcium concentrations. Caffeine is a xanthine alkaloid compound that acts as a stimulant in humans. ...


Role in disease

RyR1 mutations are associated with malignant hyperthermia and central core disease. RyR2 mutations play a role in stress-induced polymorphic ventricular tachycardia (a form of cardiac arrhythmia) and ARVD.[1] It has also been shown that levels of type RyR3 are greatly increased in PC12 cells overexpressing mutant human Presenilin 1, and in brain tissue in knockin mice that express mutant Presenilin 1 at normal levels, and thus may play a role in the pathogenesis of neurodegenerative diseases, like Alzheimer's disease. For linguistic mutation, see Apophony. ... Malignant hyperthermia (MH or MHS for malignant hyperthermia syndrome, or malignant hyperpyrexia due to anesthesia) is a rare life-threatening condition that is triggered by exposure to drugs used for general anaesthesia, such as volatile anaesthetics or the depolarizing muscle relaxant suxamethonium chloride. ... In biology, polymorphism can be defined as the occurrence in the same habitat of two or more forms of a trait in such frequencies that the rarer cannot be maintained by recurrent mutation alone. ... Ventricular tachycardia (V-tach or VT) is a fast rhythm that originates in one of the ventricles of the heart. ... Cardiac arrhythmia is any of a group of conditions in which the electrical activity of the heart is irregular or is faster or slower than normal. ... Arrhythmogenic right ventricular dysplasia (ARVD, also known as arrhythmogenic right ventricular cardiomyopathy or ARVC) is a type of nonischemic cardiomyopathy that involves primarily the right ventricle. ... Neurodegeneration is progressive loss of structure or function of neurons, including death of neurons. ...


The presence of antibodies against ryanodine receptors in blood serum has also been associated with myasthenia gravis. Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... Blood plasma is a component of blood. ... Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. ...


References

  1. ^ a b c Zucchi R, Ronca-Testoni S. The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs, and disease states. Pharmacol Rev 1997;49:1-51. PMID 9085308.
  2. ^ Fabiato A (1983). "Calcium-induced calcium release of calcium from the cardiac sarcoplasmic reticulum". Am J Physiol 245 (1): C1-C14. PMID 6346892. 
  3. ^ Cheng H, Lederer WJ, Cannell MB (1993). "Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science 262 (5134): 740-744. PMID 8235594. 
  4. ^ Vites A, Pappano A (1994). "Distinct modes of inhibition by ruthenium red and ryanodine of calcium-induced calcium release in avian atrium". J Pharmacol Exp Ther 268 (3): 1476-84. PMID 7511166. 
  5. ^ Xu L, Tripathy A, Pasek D, Meissner G. "Potential for pharmacology of ryanodine receptor/calcium release channels". Ann N Y Acad Sci 853: 130-48. PMID 10603942. 
  6. ^ Wang Y, Zheng Y, Mei Q, Wang Q, Collier M, Fleischer S, Xin H, Kotlikoff M (2004). "FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells". Am J Physiol Cell Physiol 286 (3): C538-46. PMID 14592808. 
  7. ^ Tu J, Xiao B, Yuan J, Lanahan A, Leoffert K, Li M, Linden D, Worley P (1998). "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors". Neuron 21 (4): 717-26. PMID 9808459. 

External links

  • MeSH Ryanodine+Receptor

  Results from FactBites:
 
ION TRANSPORT antibodies ( RYANODINE RECEPTORS ) from Research Diagnostics Inc (639 words)
Background: The Ryanodine receptor is the channel responsible for the release of Calcium from the sarcoplasmic reticulum in muscle cells and also plays a role in Ca2+ regulation in non-muscle cells.
The Ryanodine receptor exists as a homotetramer and is predicted to have a short cytoplasmic C-terminus and 4-10 transmembrane domains with the remainder of the protein termed the "foot" region, located in the cytoplasm between the T-tubule and the Sr.
-P.S. McPherson and K.P. Campbell, The Ryanodine Receptor/Ca2+
  More results at FactBites »

 
 

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