RYR2

Summary

Gene Symbol: RYR2
Description: ryanodine receptor 2
Alias: ARVC2, ARVD2, RYR-2, RyR, VTSIP, ryanodine receptor 2, cardiac muscle ryanodine receptor-calcium release channel, cardiac-type ryanodine receptor, islet-type ryanodine receptor, kidney-type ryanodine receptor, ryanodine receptor 2 (cardiac), type 2 ryanodine receptor
Species: human
Products:     RYR2

Top Publications

  1. Marx S, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, et al. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell. 2000;101:365-76 pubmed
    ..The channel is a tetramer comprised of four type 2 RyR polypeptides (RyR2) and four FK506 binding proteins (FKBP12.6)...
  2. Marx S, Reiken S, Hisamatsu Y, Gaburjakova M, Gaburjakova J, Yang Y, et al. Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers. J Cell Biol. 2001;153:699-708 pubmed
    ..Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents ..
  3. Tiso N, Salamon M, Bagattin A, Danieli G, Argenton F, Bortolussi M. The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochem Biophys Res Commun. 2002;299:594-8 pubmed
    Arrhythmogenic right ventricular dysplasia/cardiomyopathy type 2 (ARVD2, OMIM 600996) and stress-induced polymorphic ventricular tachycardia (VTSIP, OMIM 604772) are two cardiac diseases causing juvenile sudden death, both associated ..
  4. Johnson J, Kuang S, Misler S, Polonsky K. Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion. FASEB J. 2004;18:878-80 pubmed
    ..In diabetes, the expression and function of ryanodine receptor (RyR) Ca2+ release channels are reduced...
  5. Lehnart S, Wehrens X, Laitinen P, Reiken S, Deng S, Cheng Z, et al. Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak. Circulation. 2004;109:3208-14 pubmed
    ..exercise-induced arrhythmias and sudden cardiac death due to missense mutations in the cardiac ryanodine receptor (RyR2), an intracellular Ca2+ release channel required for excitation-contraction coupling in the heart...
  6. Tiso N, Stephan D, Nava A, Bagattin A, Devaney J, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10:189-94 pubmed
    Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death...
  7. Wang R, Bolstad J, Kong H, Zhang L, Brown C, Chen S. The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating. J Biol Chem. 2004;279:3635-42 pubmed
    ..of mutations of each residue within the 24-amino acid TM10 sequence of the mouse cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+)...
  8. Wehrens X, Lehnart S, Reiken S, Marks A. Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor. Circ Res. 2004;94:e61-70 pubmed
    The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling...
  9. Johnson J, Han Z, Otani K, Ye H, Zhang Y, Wu H, et al. RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. J Biol Chem. 2004;279:24794-802 pubmed
    Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis...

More Information

Publications102 found, 100 shown here

  1. Tunwell R, Wickenden C, Bertrand B, Shevchenko V, Walsh M, Allen P, et al. The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. Biochem J. 1996;318 ( Pt 2):477-87 pubmed
    ..Six hydrophobic stretches, which are present within the hRyR-2 C-terminal 500 amino acids and are conserved in all RyR sequences, may be involved in forming the transmembrane domain that constitutes the Ca(2+)-conducting pathway, in ..
  2. Priori S, Napolitano C, Tiso N, Memmi M, Vignati G, Bloise R, et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001;103:196-200 pubmed
    ..We demonstrated that, in agreement with our hypothesis, hRyR2 is a gene responsible for catecholaminergic polymorphic ventricular tachycardia. ..
  3. George C, Higgs G, Lai F. Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ Res. 2003;93:531-40 pubmed
    Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction...
  4. Stewart R, Zissimopoulos S, Lai F. Oligomerization of the cardiac ryanodine receptor C-terminal tail. Biochem J. 2003;376:795-9 pubmed
    ..We explored these possibilities for RyR2 (cardiac RyR) using the yeast two-hybrid interaction assay and in vitro translation followed by immunoprecipitation ..
  5. Laitinen P, Swan H, Kontula K. Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms. Eur J Hum Genet. 2003;11:888-91 pubmed
    Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting ..
  6. Bhuiyan Z, van den Berg M, van Tintelen J, Bink Boelkens M, Wiesfeld A, Alders M, et al. Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features. Circulation. 2007;116:1569-76 pubmed
    ..Conventional polymerase chain reaction-based screening did not reveal a mutation in either the Ryanodine receptor 2 gene (RYR2) or ACTN2, the most plausible candidate genes in the region of interest...
  7. Thomas N, Maxwell C, Mukherjee S, Williams A. Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel dysfunction. FEBS Lett. 2010;584:2153-60 pubmed publisher
    Mutations in RyR2 are causative of an inherited disorder which often results in sudden cardiac death...
  8. Denda S, Kumamoto J, Takei K, Tsutsumi M, Aoki H, Denda M. Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis. J Invest Dermatol. 2012;132:69-75 pubmed publisher
    ..In the present study, we investigated the expression of RyR in human epidermis...
  9. Otsu K, Willard H, Khanna V, Zorzato F, Green N, MacLennan D. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem. 1990;265:13472-83 pubmed
    ..The two receptors are clearly the products of separate genes, and the gene encoding the cardiac muscle ryanodine receptor was localized to chromosome 1. ..
  10. Tester D, Dura M, Carturan E, Reiken S, Wronska A, Marks A, et al. A mechanism for sudden infant death syndrome (SIDS): stress-induced leak via ryanodine receptors. Heart Rhythm. 2007;4:733-9 pubmed
    ..Mutations in the RyR2-encoded cardiac ryanodine receptor cause the highly lethal catecholaminergic polymorphic ventricular tachycardia (..
  11. Medeiros Domingo A, Bhuiyan Z, Tester D, Hofman N, Bikker H, van Tintelen J, et al. The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame. J Am Coll Cardiol. 2009;54:2065-74 pubmed publisher
    This study was undertaken to determine the spectrum and prevalence of mutations in the RYR2-encoded cardiac ryanodine receptor in cases with exertional syncope and normal corrected QT interval (QTc)...
  12. George C, Jundi H, Thomas N, Scoote M, Walters N, Williams A, et al. Ryanodine receptor regulation by intramolecular interaction between cytoplasmic and transmembrane domains. Mol Biol Cell. 2004;15:2627-38 pubmed
    ..6 and caffeine. The impact of coexpressing dsRed-tagged cytoplasmic domains of RyR2 on intracellular Ca(2+) phenotype was assessed using confocal microscopy coupled with parallel determination of in ..
  13. Takasawa S, Kuroki M, Nata K, Noguchi N, Ikeda T, Yamauchi A, et al. A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene. Biochem Biophys Res Commun. 2010;397:140-5 pubmed publisher
    ..screening a rat islet cDNA library, we isolated a novel RyR cDNA (the islet-type RyR), which is generated from the RyR2 gene by alternative splicing of exons 4 and 75...
  14. Marciante K, Durda J, Heckbert S, Lumley T, Rice K, McKnight B, et al. Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011;21:280-8 pubmed publisher
    ..001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P=1.74E-07)...
  15. Meli A, Refaat M, Dura M, Reiken S, Wronska A, Wojciak J, et al. A novel ryanodine receptor mutation linked to sudden death increases sensitivity to cytosolic calcium. Circ Res. 2011;109:281-90 pubmed publisher
    Mutations in the cardiac type 2 ryanodine receptor (RyR2) have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT)...
  16. Laitinen P, Brown K, Piippo K, Swan H, Devaney J, Brahmbhatt B, et al. Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation. 2001;103:485-90 pubmed
    ..have missense mutations in the cardiac sarcoplasmic reticulum calcium release channel (ryanodine receptor type 2 [RyR2])...
  17. Marjamaa A, Laitinen Forsblom P, Wronska A, Toivonen L, Kontula K, Swan H. Ryanodine receptor (RyR2) mutations in sudden cardiac death: studies in extended pedigrees and phenotypic characterization in vitro. Int J Cardiol. 2011;147:246-52 pubmed publisher
    Catecholaminergic polymorphic ventricular tachycardia caused by mutations in the RyR2 gene manifests as severe arrhythmias, and may provide a candidate for sudden cardiac deaths...
  18. Matus M, Kucerova D, Kruzliak P, Adameova A, Doka G, Turcekova K, et al. Upregulation of SERCA2a following short-term ACE inhibition (by enalaprilat) alters contractile performance and arrhythmogenicity of healthy myocardium in rat. Mol Cell Biochem. 2015;403:199-208 pubmed publisher
    ..1C subunit) were measured by Western blot; mRNA levels of L-type calcium channel (Cacna1c), ryanodine receptor (Ryr2) and potassium channels Kcnh2 and Kcnq1 were measured by qRT-PCR...
  19. Seara F, Barbosa R, de Oliveira D, Gran da Silva D, Carvalho A, Freitas Ferreira A, et al. Administration of anabolic steroid during adolescence induces long-term cardiac hypertrophy and increases susceptibility to ischemia/reperfusion injury in adult Wistar rats. J Steroid Biochem Mol Biol. 2017;171:34-42 pubmed publisher
    ..by mRNA levels of ?-myosin heavy chain (MHC), ?MHC and brain-derived natriuretic peptide (BNP), ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) by quantitative RT-PCR (qRT-PCR)...
  20. Ho H, Thambidorai S, Knollmann B, Billman G, Györke S, Kalyanasundaram A. Accentuated vagal antagonism paradoxically increases ryanodine receptor calcium leak in long-term exercised Calsequestrin2 knockout mice. Heart Rhythm. 2018;15:430-441 pubmed publisher
    ..In parallel, ventricular ryanodine receptor (RyR2) protein expression increased, whereas protein kinase A- and calmodulin-dependent protein kinase II-mediated ..
  21. Liu Z, Cai H, Zhu H, Toque H, Zhao N, Qiu C, et al. Protein kinase RNA-like endoplasmic reticulum kinase (PERK)/calcineurin signaling is a novel pathway regulating intracellular calcium accumulation which might be involved in ventricular arrhythmias in diabetic cardiomyopathy. Cell Signal. 2014;26:2591-600 pubmed publisher
    ..6 disassociation from ryanodine receptor 2 (RyR2)...
  22. Yang J, Zhang R, Jiang X, Lv J, Li Y, Ye H, et al. Toll-like receptor 4-induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca2+ leakage promote cardiac contractile dysfunction in sepsis. J Biol Chem. 2018;293:794-807 pubmed publisher
    ..In the LPS-treated cardiomyocytes, mitochondrial reactive oxygen species and oxidative stress in RyR2 were increased, whereas the levels of the RyR2-associated FK506-binding protein 1B (FKBP12.6) were decreased...
  23. Song T, Zheng Y, Wang Y. Cross Talk Between Mitochondrial Reactive Oxygen Species and Sarcoplasmic Reticulum Calcium in Pulmonary Arterial Smooth Muscle Cells. Adv Exp Med Biol. 2017;967:289-298 pubmed publisher
    ..Ryanodine receptor-2 (RyR2)/Ca2+ release channel on the sarcoplasmic reticulum (SR) serves as a most valuable player in the ..
  24. Payne A, Gerdes B, Naumchuk Y, McCalley A, Kaja S, Koulen P. Presenilins regulate the cellular activity of ryanodine receptors differentially through isotype-specific N-terminal cysteines. Exp Neurol. 2013;250:143-50 pubmed publisher
    ..cytosolic N-terminal domain fragment (NTF) of PS to intracellular Ca(2+) release channels, ryanodine receptors (RyR), controls Ca(2+) release from the ER...
  25. Ferrantini C, Coppini R, Scellini B, Ferrara C, Pioner J, Mazzoni L, et al. R4496C RyR2 mutation impairs atrial and ventricular contractility. J Gen Physiol. 2016;147:39-52 pubmed publisher
    Ryanodine receptor (RyR2) is the major Ca(2+) channel of the cardiac sarcoplasmic reticulum (SR) and plays a crucial role in the generation of myocardial force...
  26. Ruan J, Tulloch N, Razumova M, Saiget M, Muskheli V, Pabon L, et al. Mechanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue. Circulation. 2016;134:1557-1567 pubmed
    ..Supporting this notion, we found expression of RYR2 (Ryanodine Receptor 2) and SERCA2 further increased by combined static stress and electric stimulation...
  27. Belkaya S, Kontorovich A, Byun M, Mulero Navarro S, Bajolle F, Cobat A, et al. Autosomal Recessive Cardiomyopathy Presenting as Acute Myocarditis. J Am Coll Cardiol. 2017;69:1653-1665 pubmed publisher
    ..heterozygous) nonsynonymous or splice-site variations in 6 cardiomyopathy-associated genes (BAG3, DSP, PKP2, RYR2, SCN5A, or TNNI3)...
  28. Shah A, Matsumura N, Quon A, Morton J, Dyck J, Davidge S. Cardiovascular susceptibility to in vivo ischemic myocardial injury in male and female rat offspring exposed to prenatal hypoxia. Clin Sci (Lond). 2017;131:2303-2317 pubmed publisher
    ..Prenatal hypoxia increased cardiac ryanodine receptor 2 (RYR2) protein levels, while MI reduced RYR2 in only male offspring...
  29. George C, Rogers S, Bertrand B, Tunwell R, Thomas N, Steele D, et al. Alternative splicing of ryanodine receptors modulates cardiomyocyte Ca2+ signaling and susceptibility to apoptosis. Circ Res. 2007;100:874-83 pubmed
    Ca(2+) release via type 2 ryanodine receptors (RyR2) regulates cardiac function...
  30. Meissner G, Pasek D, Yamaguchi N, Ramachandran S, Dokholyan N, Tripathy A. Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels. Proteins. 2009;74:207-11 pubmed publisher
    The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium release channels contain a single, conserved calmodulin (CaM) binding domain, yet are differentially regulated by CaM...
  31. Perry S, Barbieri J, Tong N, Polesskaya O, Pudasaini S, Stout A, et al. Human immunodeficiency virus-1 Tat activates calpain proteases via the ryanodine receptor to enhance surface dopamine transporter levels and increase transporter-specific uptake and Vmax. J Neurosci. 2010;30:14153-64 pubmed publisher
    ..factor (Tat) acutely disrupts mitochondrial and endoplasmic reticulum calcium homeostasis via ryanodine receptor (RyR) activation...
  32. Tang Y, Tian X, Wang R, Fill M, Chen S. Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res. 2012;110:968-77 pubmed publisher
    Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) have been associated with both cardiac arrhythmias and cardiomyopathies...
  33. Nyegaard M, Overgaard M, Søndergaard M, Vranas M, Behr E, Hildebrandt L, et al. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death. Am J Hum Genet. 2012;91:703-12 pubmed publisher
    ..Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all ..
  34. Shiels H, Sitsapesan R. Is there something fishy about the regulation of the ryanodine receptor in the fish heart?. Exp Physiol. 2015;100:1412-20 pubmed publisher
    ..Here, we focus on the cardiac SR Ca(2+)-release channel (RyR2) in fish and ask whether it may be regulated in a different manner from the mammalian RyR2...
  35. Guo W, Sun B, Xiao Z, Liu Y, Wang Y, Zhang L, et al. The EF-hand Ca2+ Binding Domain Is Not Required for Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor. J Biol Chem. 2016;291:2150-60 pubmed publisher
    Activation of the cardiac ryanodine receptor (RyR2) by elevating cytosolic Ca(2+) is a central step in the process of Ca(2+)-induced Ca(2+) release, but the molecular basis of RyR2 activation by cytosolic Ca(2+) is poorly defined...
  36. Bovo E, Huke S, Blatter L, Zima A. The effect of PKA-mediated phosphorylation of ryanodine receptor on SR Ca2+ leak in ventricular myocytes. J Mol Cell Cardiol. 2017;104:9-16 pubmed publisher
    Functional impact of cardiac ryanodine receptor (type 2 RyR or RyR2) phosphorylation by protein kinase A (PKA) remains highly controversial...
  37. Uebe S, Ehrlicher M, Ekici A, Behrens F, Böhm B, Homuth G, et al. Genome-wide association and targeted analysis of copy number variants with psoriatic arthritis in German patients. BMC Med Genet. 2017;18:92 pubmed publisher
    ..At three of 12 susceptibility loci with CNVs (CSMD1, IL12B, RYR2), CN variability was confirmed independently by MLPA...
  38. Farrugia A, Keyser C, Hollard C, Raul J, Muller J, Ludes B. Targeted next generation sequencing application in cardiac channelopathies: Analysis of a cohort of autopsy-negative sudden unexplained deaths. Forensic Sci Int. 2015;254:5-11 pubmed publisher
    ..75%) of our cohort in the genes KCNH2, ANK2, SCN5A and RYR2. One case, who died during psychiatric hospitalization after administration of a QT prolonging drug, showed a ..
  39. Limbu S, Hoang Trong T, Prosser B, Lederer W, Jafri M. Modeling Local X-ROS and Calcium Signaling in the Heart. Biophys J. 2015;109:2037-50 pubmed publisher
    ..The increase in Ca2+ spark rate is thought to be due to an increase in ryanodine receptor type 2 (RyR2) open probability by direct oxidation of the RyR2 protein complex...
  40. Hu S, Shen Y, Gong J, Yang Y. Effect of sophoridine on Ca²⁺ induced Ca²⁺ release during heart failure. Physiol Res. 2016;65:43-52 pubmed
    ..We investigated the Ca(2+) induced Ca(2+) transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca(2+) channel (dihydropyridine receptor, DHPR)...
  41. Chen C, Van Horn J. Developmental neurogenetics and multimodal neuroimaging of sex differences in autism. Brain Imaging Behav. 2017;11:38-61 pubmed publisher
    ..33/Yp11.31, DRD1, NLGN3, MAOA, and SHANK1 deletion have been discovered in ASD. The SNPs of genes such as RYR2, UPP2, and the androgen receptor gene have been shown to have sex-biasing factors in both girls and boys diagnosed ..
  42. Gaburjakova J, Gaburjakova M. Cardiac ryanodine receptor: Selectivity for alkaline earth metal cations points to the EF-hand nature of luminal binding sites. Bioelectrochemistry. 2016;109:49-56 pubmed publisher
    A growing body of evidence suggests that the regulation of cardiac ryanodine receptor (RYR2) by luminal Ca(2+) is mediated by luminal binding sites located on the RYR2 channel itself and/or its auxiliary protein, calsequestrin...
  43. Josephs K, Patel K, Janson C, Montagna C, McDonald T. Compound heterozygous CASQ2 mutations and long-term course of catecholaminergic polymorphic ventricular tachycardia. Mol Genet Genomic Med. 2017;5:788-794 pubmed publisher
    ..Approximately 50% of CPVT cases are caused by dominant mutations in the cardiac ryanodine receptor (RYR2) gene, <5% of cases are accounted for by recessive mutations in cardiac calsequestrin (CASQ2) or Triadin (TRDN).
  44. Ogawa Y, Kurebayashi N, Murayama T. Ryanodine receptor isoforms in excitation-contraction coupling. Adv Biophys. 1999;36:27-64 pubmed
    ..RyR1 homologue is the primary isoform in skeletal muscles, whereas in cardiac muscles it is RyR2 homologue...
  45. Xiao B, Masumiya H, Jiang D, Wang R, Sei Y, Zhang L, et al. Isoform-dependent formation of heteromeric Ca2+ release channels (ryanodine receptors). J Biol Chem. 2002;277:41778-85 pubmed publisher
    Three ryanodine receptor (RyR) isoforms, RyR1, RyR2, and RyR3, are expressed in mammalian tissues. It is unclear whether RyR isoforms are capable of forming heteromeric channels...
  46. Zhang J, Liu Z, Masumiya H, Wang R, Jiang D, Li F, et al. Three-dimensional localization of divergent region 3 of the ryanodine receptor to the clamp-shaped structures adjacent to the FKBP binding sites. J Biol Chem. 2003;278:14211-8 pubmed
    ..the structural basis of DR3 function, we have determined the location of DR3 in the three-dimensional structure of RyR2. We inserted green fluorescent protein (GFP) into the middle of the DR3 region after Thr-1874 in the sequence...
  47. Borko L, Kost an J, Zahradnikova A, Pevala V, Gasperík J, Hostinová E, et al. Human cardiac ryanodine receptor: preparation, crystallization and preliminary X-ray ANALysis of the N-terminal region. Protein Pept Lett. 2013;20:1211-6 pubmed
    Human ryanodine receptor 2 (hRyR2) is a calcium ion channel present in the membrane of the sarcoplasmic reticulum of cardiac myocytes that mediates release of calcium ions from the sarcoplasmic reticulum stores during excitation- ..
  48. Hubacek J, Adamkova V, Hrubá P, Ceska R, Vrablik M. Association between polymorphism within the RYR2 receptor and development of statin-associated myalgia/myopathy in the Czech population. Eur J Intern Med. 2015;26:367-8 pubmed publisher
  49. Oda T, Yang Y, Uchinoumi H, Thomas D, Chen Izu Y, Kato T, et al. Oxidation of ryanodine receptor (RyR) and calmodulin enhance Ca release and pathologically alter, RyR structure and calmodulin affinity. J Mol Cell Cardiol. 2015;85:240-8 pubmed publisher
    Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in heart failure (HF) and arrhythmias...
  50. Abu Omar N, Das J, Szeto V, Feng Z. Neuronal Ryanodine Receptors in Development and Aging. Mol Neurobiol. 2018;55:1183-1192 pubmed publisher
    ..All three RyR isoforms, RyR1-3, are expressed in the brain, with RyR2 predominating. RyRs are localized within the soma, axons, dendritic spines, and presynaptic terminals of neurons...
  51. Gray B, Bagnall R, Lam L, Ingles J, Turner C, Haan E, et al. A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2016;13:1652-60 pubmed publisher
    ..Mutations in the cardiac ryanodine receptor gene (RYR2) cause an autosomal dominant form of CPVT, while mutations in the cardiac calsequestrin 2 gene (CASQ2) cause an ..
  52. Pinali C, Malik N, Davenport J, Allan L, Murfitt L, Iqbal M, et al. Post-Myocardial Infarction T-tubules Form Enlarged Branched Structures With Dysregulation of Junctophilin-2 and Bridging Integrator 1 (BIN-1). J Am Heart Assoc. 2017;6: pubmed publisher
    ..Biochemical and proteomics analyses showed that the calcium release channel, ryanodine receptor 2 (RyR2), abundance is unchanged, but junctophilin-2 (JP2), important for maintaining t-t trajectory, is ..
  53. Pahlavan S, Morad M. Total internal reflectance fluorescence imaging of genetically engineered ryanodine receptor-targeted Ca2+ probes in rat ventricular myocytes. Cell Calcium. 2017;66:98-110 pubmed publisher
    ..To critically monitor ryanodine receptors' (RyR2) Ca2+ nano-domains, we combined the use of genetically engineered RyR2-targeted pericam probes, (FKBP-..
  54. Onal B, Gratz D, Hund T. Ca2+/calmodulin kinase II-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling and excitability: a mathematical modeling study. Am J Physiol Heart Circ Physiol. 2017;:ajpheart.00185.2017 pubmed publisher
    ..phospholamban (PLB), and the ryanodine receptor sarcoplasmic reticulum (SR) Ca2+ release channel (RYR2)] were incorporated into an existing well-validated computational model of the human atrial action potential...
  55. Baek S, Chung H, Song M, Bae E, Kim G, Noh C. The Complexity of Pediatric Multifocal Atrial Tachycardia and Its Prognostic Factors. Korean Circ J. 2018;48:148-158 pubmed publisher
    ..Two patients developed polymorphic ventricular tachycardia, in whom genetic analysis confirmed the presence of the RyR2 mutation several years later. MAT was controlled in 26 patients (84%) within 3.9 months (median; range, 16 days-18...
  56. Hunt D, Jones P, Wang R, Chen W, Bolstad J, Chen K, et al. K201 (JTV519) suppresses spontaneous Ca2+ release and [3H]ryanodine binding to RyR2 irrespective of FKBP12.6 association. Biochem J. 2007;404:431-8 pubmed
    ..It is believed to stabilize the closed state of the RyR2 (cardiac ryanodine receptor) by increasing its affinity for the FKBP12.6 (12...
  57. Kaartinen M, Helio T, Lehtonen A, Lahtinen A, Kärkkäinen S, Keto P, et al. Characterization of familial and sporadic arrhythmogenic right ventricular cardiomyopathy in Finland. Ann Med. 2007;39:312-8 pubmed
    ..The sporadic disease is similar to the familial one which may reflect low penetration in relatives. The proportion of familial manifestation of ARVC in Finland seems comparable to that elsewhere in Europe. ..
  58. Lahtinen A, Havulinna A, Noseworthy P, Jula A, Karhunen P, Perola M, et al. Prevalence of arrhythmia-associated gene mutations and risk of sudden cardiac death in the Finnish population. Ann Med. 2013;45:328-35 pubmed publisher
    ..0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W...
  59. Treviño L, Yang W, French D, Hunger S, Carroll W, Devidas M, et al. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet. 2009;41:1001-5 pubmed publisher
    ..86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline variants affect susceptibility to, and characteristics of, specific ALL subtypes. ..
  60. Girard T, Cavagna D, Padovan E, Spagnoli G, Urwyler A, Zorzato F, et al. B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators. J Biol Chem. 2001;276:48077-82 pubmed
    ..B-cells from MH-susceptible individuals carrying the V2168M RYR1 gene mutation were more sensitive to the RYR activator 4-chloro-m-cresol and (ii) their peripheral blood leukocytes produce more interleukin (IL)-1beta after ..
  61. Mukherjee S, Thomas N, Williams A. A mechanistic description of gating of the human cardiac ryanodine receptor in a regulated minimal environment. J Gen Physiol. 2012;140:139-58 pubmed publisher
    ..In situ, RyR2 gating is modulated by numerous physiological and pharmacological agents, and altered RyR2 function underlies the ..
  62. Lau K, Van Petegem F. Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain. Nat Commun. 2014;5:5397 pubmed publisher
    ..Here we present the crystal structures of the SPRY2 domain from RyR1 and RyR2 at 1.34-1.84 Å resolution...
  63. Kong H, Wang R, Chen W, Zhang L, Chen K, Shimoni Y, et al. Skeletal and cardiac ryanodine receptors exhibit different responses to Ca2+ overload and luminal ca2+. Biophys J. 2007;92:2757-70 pubmed
    ..In this study, we investigated the SOICR properties of HEK293 cells expressing RyR1 or RyR2. We found that HEK293 cells expressing RyR2 exhibited robust SOICR activity, whereas no SOICR activity was observed ..
  64. Kawamura M, Ohno S, Naiki N, Nagaoka I, Dochi K, Wang Q, et al. Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan. Circ J. 2013;77:1705-13 pubmed
    ..clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features ..
  65. Yamazaki D, Yamazaki T, Takeshima H. New molecular components supporting ryanodine receptor-mediated Ca(2+) release: roles of junctophilin and TRIC channel in embryonic cardiomyocytes. Pharmacol Ther. 2009;121:265-72 pubmed publisher
    ..This review focuses on cardiac Ca(2+) release by discussing pathological defects of mutant cardiomyocytes lacking ryanodine receptors, junctophilins, or TRIC channels. ..
  66. Mantziari L, Vassilikos V, Anastasakis A, Kotsaka X, Paraskevaidis S, Styliadis I, et al. A de novo novel cardiac ryanodine mutation (Ser4155Tyr) associated with catecholaminergic polymorphic ventricular tachycardia. Ann Noninvasive Electrocardiol. 2013;18:571-6 pubmed publisher
    ..The girl was treated with an implantable defibrillator, metoprolol and flecainide. Over 1 year of follow-up she had no recurrence of ventricular tachycardia. ..
  67. Leong I, Sucich J, Prosser D, Skinner J, Crawford J, Higgins C, et al. Array comparative genomic hybridization identifies a heterozygous deletion of exon 3 of the RYR2 gene. Ups J Med Sci. 2015;120:190-7 pubmed publisher
    ..The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent ..
  68. Ambalavanan A, Girard S, Ahn K, Zhou S, Dionne Laporte A, Spiegelman D, et al. De novo variants in sporadic cases of childhood onset schizophrenia. Eur J Hum Genet. 2016;24:944-8 pubmed publisher
    ..Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, ..
  69. Terentyev D, Hamilton S. Regulation of sarcoplasmic reticulum Ca2+ release by serine-threonine phosphatases in the heart. J Mol Cell Cardiol. 2016;101:156-164 pubmed publisher
    ..Reversible phosphorylation of the SR Ca2+ release channel, ryanodine receptor type 2 (RyR2) is the central mechanism of regulation of Ca2+ release in cardiomyocytes...
  70. Handhle A, Ormonde C, Thomas N, Bralesford C, Williams A, Lai F, et al. Calsequestrin interacts directly with the cardiac ryanodine receptor luminal domain. J Cell Sci. 2016;129:3983-3988 pubmed
    ..sarcoplasmic reticulum (SR) Ca2+ release mediated by the quaternary complex comprising the ryanodine receptor 2 (RyR2), calsequestrin 2 (CSQ2), junctin (encoded by ASPH) and triadin...
  71. Munro M, Jayasinghe I, Wang Q, Quick A, Wang W, Baddeley D, et al. Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes. J Cell Sci. 2016;129:4388-4398 pubmed
    ..protein within it, the ryanodine receptor (RyR; in this paper, we use RyR to refer to the myocardial isoform RyR2)...
  72. Sedej S, Heinzel F, Walther S, Dybkova N, Wakula P, Groborz J, et al. Na+-dependent SR Ca2+ overload induces arrhythmogenic events in mouse cardiomyocytes with a human CPVT mutation. Cardiovasc Res. 2010;87:50-9 pubmed publisher
    Mutations in the cardiac ryanodine receptor Ca(2+) release channel, RyR2, underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited life-threatening arrhythmia...
  73. Bannister M, Thomas N, Sikkel M, Mukherjee S, Maxwell C, MacLeod K, et al. The mechanism of flecainide action in CPVT does not involve a direct effect on RyR2. Circ Res. 2015;116:1324-35 pubmed publisher
    ..efficacy of flecainide in CPVT is because of the combined actions of direct blockade of ryanodine receptors (RyR2) and Na(+) channel inhibition...
  74. Novak A, Barad L, Lorber A, Gherghiceanu M, Reiter I, Eisen B, et al. Functional abnormalities in iPSC-derived cardiomyocytes generated from CPVT1 and CPVT2 patients carrying ryanodine or calsequestrin mutations. J Cell Mol Med. 2015;19:2006-18 pubmed publisher
    ..CPVT is caused by abnormal intracellular Ca(2+) handling resulting from mutations in the RyR2 or CASQ2 genes...
  75. Wilson D, Ermentrout B, Nemec J, Salama G. A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome. Chaos. 2017;27:093940 pubmed publisher
    ..are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance...
  76. Aizawa Y, Ueda K, Komura S, Washizuka T, Chinushi M, Inagaki N, et al. A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia. Int J Cardiol. 2005;99:343-5 pubmed
    ..The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT...
  77. Lehnart S, Wehrens X, Reiken S, Warrier S, Belevych A, Harvey R, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell. 2005;123:25-35 pubmed
    ..The phosphodiesterase 4D3 (PDE4D3) was found in the cardiac ryanodine receptor (RyR2)/calcium-release-channel complex (required for excitation-contraction [EC] coupling in heart muscle)...
  78. Viitasalo M, Oikarinen L, Vaananen H, Kontula K, Toivonen L, Swan H. U-waves and T-wave peak to T-wave end intervals in patients with catecholaminergic polymorphic ventricular tachycardia, effects of beta-blockers. Heart Rhythm. 2008;5:1382-8 pubmed publisher
    ..We reviewed Holter recordings from 19 CPVT patients with a RyR2 mutation (P2328S or V4653F) and from 19 healthy unaffected subjects to record U-waves and TPE intervals as well as ..
  79. Bruno A, Huang J, Bennett D, Marr R, Hastings M, Stutzmann G. Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2012;33:1001.e1-6 pubmed publisher
    ..Here, we compare mRNA levels of the RyR2 and RyR3 isoforms as well as specific alternatively spliced variants across vulnerable brain regions from ..
  80. Arad M, Glikson M, El Ani D, Monserrat Inglesias L. A family with recurrent sudden death and no clinical clue. Ann Noninvasive Electrocardiol. 2012;17:387-93 pubmed publisher
    ..Interpretation of autopsy data, provocation testing and genetic testing in victims of sudden death and family members are discussed to correctly identify the cause and properly manage asymptomatic carriers in such families. ..
  81. Oda T, Yang Y, Nitu F, Svensson B, Lu X, Fruen B, et al. In cardiomyocytes, binding of unzipping peptide activates ryanodine receptor 2 and reciprocally inhibits calmodulin binding. Circ Res. 2013;112:487-97 pubmed publisher
    One hypothesis for elevated Ca(2+) leak through cardiac ryanodine receptors (ryanodine receptor 2 [RyR2]) in heart failure is interdomain unzipping that can enhance aberrant channel activation...
  82. Uehara A, Murayama T, Yasukochi M, Fill M, Horie M, Okamoto T, et al. Extensive Ca2+ leak through K4750Q cardiac ryanodine receptors caused by cytosolic and luminal Ca2+ hypersensitivity. J Gen Physiol. 2017;149:199-218 pubmed publisher
    Various ryanodine receptor 2 (RyR2) point mutations cause catecholamine-induced polymorphic ventricular tachycardia (CPVT), a life-threatening arrhythmia evoked by diastolic intracellular Ca2+ release dysfunction...
  83. Borchert T, Hübscher D, Guessoum C, Lam T, Ghadri J, Schellinger I, et al. Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy. J Am Coll Cardiol. 2017;70:975-991 pubmed publisher
    ..levels; and cyclic adenosine monophosphate-dependent protein kinase A-mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay...
  84. Thomas N, George C, Lai F. Role of ryanodine receptor mutations in cardiac pathology: more questions than answers?. Biochem Soc Trans. 2006;34:913-8 pubmed
    ..Recently, single-residue mutations in the cardiac RyR (RyR2) have been identified in families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a ..
  85. Ding L, Abebe T, Beyene J, Wilke R, Goldberg A, Woo J, et al. Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations. Hum Genomics. 2013;7:16 pubmed publisher
    ..b>Ryanodine receptor 2 (RYR2, a statin response-related gene) showed the strongest association in European (p value=2...
  86. Manotheepan R, Saberniak J, Danielsen T, Edvardsen T, Sjaastad I, Haugaa K, et al. Effects of individualized exercise training in patients with catecholaminergic polymorphic ventricular tachycardia type 1. Am J Cardiol. 2014;113:1829-33 pubmed publisher
    ..05). In conclusion, patients with CPVT1 benefitted from individualized ET with improved aerobic capacity and increased threshold HR for VA compared with SED patients. ..
  87. Fejzo M, Myhre R, Colodro Conde L, MacGibbon K, Sinsheimer J, Reddy M, et al. Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2). Mol Cell Endocrinol. 2017;439:308-316 pubmed publisher
    ..Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control...
  88. Song J, Kang J, Kim Y, Park S, Park K, Huh J, et al. Identification of pathogenic variants in genes related to channelopathy and cardiomyopathy in Korean sudden cardiac arrest survivors. J Hum Genet. 2017;62:615-620 pubmed publisher
    ..3%) had either a pathogenic variant or a likely pathogenic variant in MYBPC3 (n=1), MYH7 (n=1), RYR2 (n=2), or TNNT2 (n=1)...
  89. Mizuno K, Kurokawa K, Ohkuma S. Regulatory mechanisms and pathophysiological significance of IP3 receptors and ryanodine receptors in drug dependence. J Pharmacol Sci. 2013;123:306-11 pubmed
    ..Although previous reports showed that the most important regulators of both RyR and IP3R channel functions are changes in the intracellular Ca(2+) concentration and in phosphorylation of these ..
  90. Tsai F, Lin Y, Chang S, Chang G, Hsu Y, Lin Y, et al. Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis. Int J Cardiol. 2016;222:104-112 pubmed publisher
    ..Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. ..
  91. Roston T, Cunningham T, Sanatani S. Advances in the diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia. Cardiol Young. 2017;27:S49-S56 pubmed publisher
    ..Most cases are related to variants in the gene encoding for ryanodine receptor-2 (RyR2), which mediates calcium-induced calcium release. Up to half of cases remain genetically elusive...
  92. D Ovidio C, Carnevale A, Grassi V, Rosato E, Del Olmo B, Coll M, et al. Sudden death due to catecholaminergic polymorphic ventricular tachycardia following negative stress-test outcome: genetics and clinical implications. Forensic Sci Med Pathol. 2017;13:217-225 pubmed publisher
    ..It was possible to detect a novel, previously undescribed, variant in the RYR2 gene...