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

Top Publications

  1. pmc Mapping the ryanodine receptor FK506-binding protein subunit using fluorescence resonance energy transfer
    Razvan L Cornea
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Biol Chem 285:19219-26. 2010
  2. pmc In vitro modeling of ryanodine receptor 2 dysfunction using human induced pluripotent stem cells
    Azra Fatima
    Institute for Neurophysiology, University of Cologne, Robert Koch Strasse 39, Cologne, Germany
    Cell Physiol Biochem 28:579-92. 2011
  3. pmc 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
    Seth W Perry
    Center for Neural Development and Disease, Department of Neurology, Child Neurology Division, Graduate Program in Pathology, and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Neurosci 30:14153-64. 2010
  4. ncbi Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers
    Barbara Bauce
    Department of Cardiology, University of Padua Medical School, Via A Gabelli, 86 35121 Padua, Italy
    J Am Coll Cardiol 40:341-9. 2002
  5. pmc Ca(2+)-calmodulin can activate and inactivate cardiac ryanodine receptors
    C Sigalas
    Department of Physiology and Pharmacology and Bristol Heart Institute, University of Bristol, Bristol, UK
    Br J Pharmacol 156:794-806. 2009
  6. pmc Effects of CaMKII-mediated phosphorylation of ryanodine receptor type 2 on islet calcium handling, insulin secretion, and glucose tolerance
    Sayali S Dixit
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 8:e58655. 2013
  7. ncbi Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling
    Jens H Westhoff
    Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
    Cell Calcium 34:261-9. 2003
  8. ncbi Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum
    K Otsu
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 265:13472-83. 1990
  9. pmc The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis
    R E Tunwell
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, U K
    Biochem J 318:477-87. 1996
  10. ncbi PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Cell 101:365-76. 2000

Research Grants

  1. RAZVAN LIVIU CORNEA; Fiscal Year: 2016
  2. Michael Fill; Fiscal Year: 2016
  3. Sandor Gyorke; Fiscal Year: 2016
  4. Isoform-Specific Regulation of Skeletal Muscle Calcium Channel by Calmodulin
    Naohiro Yamaguchi; Fiscal Year: 2013
  5. Sandor Gyorke; Fiscal Year: 2016
  6. ALLOSTERIC SITE STRUCTURES OF CARDIOVASCULAR CHANNELS
    Arthur Karlin; Fiscal Year: 2011
  7. WILLIAM JONATHAN LEDERER; Fiscal Year: 2014
  8. Structural Basis of Dysfunctional Calcium Release Channels in Heart Disease
    Zheng Liu; Fiscal Year: 2013
  9. RAIMOND LESTER WINSLOW; Fiscal Year: 2015
  10. Function and regulation of elemental Ca2+ signaling in urethral smooth muscle
    Ronghua Zhuge; Fiscal Year: 2013

Detail Information

Publications207 found, 100 shown here

  1. pmc Mapping the ryanodine receptor FK506-binding protein subunit using fluorescence resonance energy transfer
    Razvan L Cornea
    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Biol Chem 285:19219-26. 2010
    ..To investigate the structural basis of FKBP interactions with the RyR1 and RyR2 isoforms, we used site-directed fluorescent labeling of FKBP12...
  2. pmc In vitro modeling of ryanodine receptor 2 dysfunction using human induced pluripotent stem cells
    Azra Fatima
    Institute for Neurophysiology, University of Cologne, Robert Koch Strasse 39, Cologne, Germany
    Cell Physiol Biochem 28:579-92. 2011
    ..CPVT1) is an inherited cardiac disorder that is caused by mutations in the cardiac ryanodine receptor type 2 gene (RYR2) and is characterized by stress-induced ventricular arrhythmia that can lead to sudden cardiac death in young ..
  3. pmc 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
    Seth W Perry
    Center for Neural Development and Disease, Department of Neurology, Child Neurology Division, Graduate Program in Pathology, and Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Neurosci 30:14153-64. 2010
    ..factor (Tat) acutely disrupts mitochondrial and endoplasmic reticulum calcium homeostasis via ryanodine receptor (RyR) activation...
  4. ncbi Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers
    Barbara Bauce
    Department of Cardiology, University of Padua Medical School, Via A Gabelli, 86 35121 Padua, Italy
    J Am Coll Cardiol 40:341-9. 2002
    We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death.
  5. pmc Ca(2+)-calmodulin can activate and inactivate cardiac ryanodine receptors
    C Sigalas
    Department of Physiology and Pharmacology and Bristol Heart Institute, University of Bristol, Bristol, UK
    Br J Pharmacol 156:794-806. 2009
    Ca(2+)-calmodulin (Ca(2+)CaM) is widely accepted as an inhibitor of cardiac ryanodine receptors (RyR2); however, the effects of physiologically relevant CaM concentrations have not been fully investigated.
  6. pmc Effects of CaMKII-mediated phosphorylation of ryanodine receptor type 2 on islet calcium handling, insulin secretion, and glucose tolerance
    Sayali S Dixit
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 8:e58655. 2013
    ..CaMKII is known to phosphorylate ryanodine receptor 2 (RyR2), an intracellular Ca(2+)-release channel implicated in Ca(2+)-dependent steps of insulin secretion...
  7. ncbi Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling
    Jens H Westhoff
    Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
    Cell Calcium 34:261-9. 2003
    ..Vesl-1L/Homer-1c (V-1L), reduces the function of the intracellular calcium channel ryanodine receptor type 2 (RyR2). In contrast, Vesl-1S/Homer-1a (V-1S) had no effect on RyR2 function but reversed the effects of V-1L...
  8. ncbi Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum
    K Otsu
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 265:13472-83. 1990
    ..The two receptors are clearly the products of separate genes, and the gene encoding the cardiac muscle ryanodine receptor was localized to chromosome 1...
  9. pmc The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis
    R E Tunwell
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, U K
    Biochem J 318:477-87. 1996
    ..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 ..
  10. ncbi PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    Cell 101:365-76. 2000
    ..The channel is a tetramer comprised of four type 2 RyR polypeptides (RyR2) and four FK506 binding proteins (FKBP12.6)...
  11. ncbi Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia
    P J Laitinen
    Department of Medicine, University of Helsinki, Helsinki, Finland
    Circulation 103:485-90. 2001
    ..In the present study, we demonstrate that patients with familial polymorphic ventricular tachycardia have missense mutations in the cardiac sarcoplasmic reticulum calcium release channel (ryanodine receptor type 2 [RyR2]).
  12. ncbi Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2)
    N Tiso
    Department of Biology, University of Padova, 35121 Padova, Italy
    Hum Mol Genet 10:189-94. 2001
    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...
  13. ncbi Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia
    S G Priori
    Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy
    Circulation 103:196-200. 2001
    ....
  14. pmc Phosphorylation-dependent regulation of ryanodine receptors: a novel role for leucine/isoleucine zippers
    S O Marx
    Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th St, New York, NY 10032, USA
    J Cell Biol 153:699-708. 2001
    ..Activation of kinases and phosphatases bound to RyR2 via LZs regulates phosphorylation of the channel, and disruption of kinase binding via LZ motifs prevents ..
  15. ncbi The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations
    Natascia Tiso
    Department of Biology, University of Padova, Via U Bassi 58 B, I 35131 Padua, Italy
    Biochem Biophys Res Commun 299:594-8. 2002
    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 ..
  16. ncbi Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes
    Christopher H George
    Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, UK
    Circ Res 93:531-40. 2003
    Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction...
  17. pmc Oligomerization of the cardiac ryanodine receptor C-terminal tail
    Richard Stewart
    Wales Heart Research Institute, Department of Cardiology, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK
    Biochem J 376:795-9. 2003
    ..We explored these possibilities for RyR2 (cardiac RyR) using the yeast two-hybrid interaction assay and in vitro translation followed by immunoprecipitation ..
  18. ncbi Molecular genetics of exercise-induced polymorphic ventricular tachycardia: identification of three novel cardiac ryanodine receptor mutations and two common calsequestrin 2 amino-acid polymorphisms
    Päivi J Laitinen
    Department of Medicine and Biomedicum Helsinki, Helsinki, Finland
    Eur J Hum Genet 11:888-91. 2003
    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 ..
  19. ncbi The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating
    Ruiwu Wang
    Cardiovascular Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 279:3635-42. 2004
    ..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+)...
  20. ncbi Ca2+/calmodulin-dependent protein kinase II phosphorylation regulates the cardiac ryanodine receptor
    Xander H T Wehrens
    Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circ Res 94:e61-70. 2004
    The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling...
  21. ncbi Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion
    James D Johnson
    Division of Metabolism, Department of Internal Medicine, Washington University School of Medicine, Box 8126, 8831 Wohl Clinic, 660 S Euclid, St Louis, MO 63110, USA
    FASEB J 18:878-80. 2004
    ..In diabetes, the expression and function of ryanodine receptor (RyR) Ca2+ release channels are reduced...
  22. ncbi RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets
    James D Johnson
    Department of Internal Medicine, Washington University, St Louis, Missouri 63110, USA
    J Biol Chem 279:24794-802. 2004
    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...
  23. pmc Ryanodine receptor regulation by intramolecular interaction between cytoplasmic and transmembrane domains
    Christopher H George
    Wales Heart Research Institute, Department of Cardiology, University of Wales College of Medicine, Cardiff, United Kingdom CF14 4XN
    Mol Biol Cell 15:2627-38. 2004
    ..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 ..
  24. ncbi Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak
    Stephan E Lehnart
    Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 W 168th St, P and S 9 401, Box 65, New York, NY 10032, USA
    Circulation 109:3208-14. 2004
    ..is characterized by 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.
  25. pmc A mechanism for sudden infant death syndrome (SIDS): stress-induced leak via ryanodine receptors
    David J Tester
    Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55901, USA
    Heart Rhythm 4:733-9. 2007
    ..Mutations in the RyR2-encoded cardiac ryanodine receptor cause the highly lethal catecholaminergic polymorphic ventricular tachycardia (..
  26. ncbi Expanding spectrum of human RYR2-related disease: new electrocardiographic, structural, and genetic features
    Zahurul A Bhuiyan
    Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, The Netherlands
    Circulation 116:1569-76. 2007
    ..Additional features include baseline bradycardia and, in some patients, right ventricular fatty displacement. The clinical spectrum is expanded by the 2 families described here...
  27. doi Ryanodine receptor (RyR2) mutations in sudden cardiac death: studies in extended pedigrees and phenotypic characterization in vitro
    Annukka Marjamaa
    Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
    Int J Cardiol 147:246-52. 2011
    Catecholaminergic polymorphic ventricular tachycardia caused by mutations in the RyR2 gene manifests as severe arrhythmias, and may provide a candidate for sudden cardiac deaths.
  28. pmc 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 muta
    Argelia Medeiros-Domingo
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Am Coll Cardiol 54:2065-74. 2009
    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).
  29. doi Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel dysfunction
    N Lowri Thomas
    Department of Cardiology, Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    FEBS Lett 584:2153-60. 2010
    Mutations in RyR2 are causative of an inherited disorder which often results in sudden cardiac death...
  30. doi A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene
    Shin Takasawa
    Department of Biochemistry, Nara Medical University, Kashihara 634 8521, Japan
    Biochem Biophys Res Commun 397:140-5. 2010
    ..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...
  31. pmc Cerivastatin, genetic variants, and the risk of rhabdomyolysis
    Kristin D Marciante
    Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA
    Pharmacogenet Genomics 21:280-8. 2011
    ..The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis...
  32. pmc A novel ryanodine receptor mutation linked to sudden death increases sensitivity to cytosolic calcium
    Albano C Meli
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA
    Circ Res 109:281-90. 2011
    Mutations in the cardiac type 2 ryanodine receptor (RyR2) have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT)...
  33. doi Ryanodine receptors are expressed in epidermal keratinocytes and associated with keratinocyte differentiation and epidermal permeability barrier homeostasis
    Sumiko Denda
    Shiseido Innovative Science Research and Development Center, Yokohama, Japan
    J Invest Dermatol 132:69-75. 2012
    ..In the present study, we investigated the expression of RyR in human epidermis...
  34. ncbi Composite polymorphisms in the ryanodine receptor 2 gene associated with arrhythmogenic right ventricular cardiomyopathy
    Hendrik Milting
    Herz und Diabeteszentrum NRW, Klinik der Ruhr Universität Bochum, Erich und Hanna Klessmann Institut für Kardiovaskuläre Forschung und Entwicklung, GeorgStr 11, 32545 Bad Oeynhausen, Germany
    Cardiovasc Res 71:496-505. 2006
    Mutations in the cardiac ryanodine receptor (RYR2) gene have been reported to cause arrhythmogenic right ventricular cardiomyopathy (ARVC). The molecular mechanisms by which genetic modifications lead to ARVC are still not well understood.
  35. ncbi FK506-binding protein (FKBP12) regulates ryanodine receptor-evoked Ca2+ release in colonic but not aortic smooth muscle
    Debbi MacMillan
    Division of Physiology and Pharmacology, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
    Cell Calcium 43:539-49. 2008
    ..myocytes, co-immunoprecipitation techniques established that FKBP12 and calcineurin each associated with the RyR2 receptor isoform (the main isoform in this tissue)...
  36. ncbi Intracellular calcium-release channels: regulators of cell life and death
    A R Marks
    Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
    Am J Physiol 272:H597-605. 1997
    ..Three forms of RyR have been identified: RyR1, expressed predominantly in skeletal muscle; RyR2, expressed predominantly in cardiac muscle; and RyR3, expressed in specialized muscles and nonmuscle tissues ..
  37. ncbi Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia
    Silvia G Priori
    Molecular Cardiology, IRCCS Fondazione S Maugeri, University of Pavia, Pavia, Italy
    Circulation 106:69-74. 2002
    Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart...
  38. pmc Three-dimensional visualization of FKBP12.6 binding to an open conformation of cardiac ryanodine receptor
    Manjuli Rani Sharma
    Wadsworth Center, New York State Department of Health, School of Public Health, State University of New York at Albany, Albany, New York 12201 0509, USA
    Biophys J 90:164-72. 2006
    The cardiac isoform of the ryanodine receptor (RyR2) from dog binds predominantly a 12.6-kDa isoform of the FK506-binding protein (FKBP12.6), whereas RyR2 from other species binds both FKBP12.6 and the closely related isoform FKBP12...
  39. ncbi Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor-mediated Ca(2+) leak from the sarcoplasmic reticulum and increases contractility
    J Prestle
    Department of Cardiology and Pneumology, Georg August University Goettingen, Goettingen, Germany
    Circ Res 88:188-94. 2001
    ..tightly associated with the cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel (ryanodine receptor type 2 [RyR2]), but the physiological function of FKBP12.6 is unclear...
  40. ncbi Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death
    Dawei Jiang
    Department of Physiology and Biophysics, University of Calgary, Alberta, Canada
    Circ Res 97:1173-81. 2005
    ..6-RyR2 interaction. Our data indicate that enhanced SOICR activity and luminal Ca2+ activation represent common defects of RyR2 mutations associated with VT and sudden death. A mechanistic model for CPVT/ARVD2 is proposed.
  41. ncbi Overexpression of FK-506 binding protein 12.0 modulates excitation contraction coupling in adult rabbit ventricular cardiomyocytes
    Tim Seidler
    Department of Cardiology and Pneumology, Georg August University Goettingen, Germany
    Circ Res 101:1020-9. 2007
    ..6+/-0.4 fold, n=5). FKBP12.0 association with rabbit cardiac ryanodine receptor (RyR2) was not detected by immunoprecipitation. However, glutathione S-transferase pull-down experiments indicated FKBP12...
  42. pmc Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor
    Hitoshi Uchinoumi
    Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1 1 1 Minamikogushi, Ube, Yamaguchi, 755 8505, Japan
    Circ Res 106:1413-24. 2010
    ..tachycardia (CPVT) is caused by a single point mutation in a well-defined region of the cardiac type 2 ryanodine receptor (RyR)2...
  43. ncbi Mechanisms of abnormal calcium homeostasis in mutations responsible for catecholaminergic polymorphic ventricular tachycardia
    Vivek Iyer
    Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Circ Res 100:e22-31. 2007
    ..ventricular tachycardia, the first located in calsequestrin (CSQN2) and the second in the ryanodine receptor (RyR2)...
  44. pmc Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia
    Marina Cerrone
    Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
    Circ Res 101:1039-48. 2007
    ..Catecholaminergic polymorphic VT is caused by enhanced Ca2+ release through defective ryanodine receptor (RyR2) channels...
  45. pmc Increased Ca2+ sensitivity of the ryanodine receptor mutant RyR2R4496C underlies catecholaminergic polymorphic ventricular tachycardia
    Maria Fernandez-Velasco
    Institut National de la Sante et de la Recherche Medicale, U637, Universite de Montpellier, Montpellier, France
    Circ Res 104:201-9, 12p following 209. 2009
    Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease...
  46. ncbi Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations
    Heikki Swan
    Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
    J Cardiovasc Electrophysiol 16:162-6. 2005
    Calcium channel antagonism in RyR2 defects.
  47. ncbi Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor
    Marina Cerrone
    Molecular Cardiology, IRCCS Fondazione S Maugeri, Pavia, Italy
    Circ Res 96:e77-82. 2005
    ..The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor...
  48. ncbi RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle
    Nicolas Fritz
    CNRS UMR 5017, Laboratoire de Signalisation et Interactions Cellulaires, Universite Bordeaux 2, Bordeaux, France
    J Cell Sci 120:3784-91. 2007
    ..We show that RyR1 is required for depolarization-induced Ca(2+) sparks, whereas RyR2 and RyR3 are sufficient for spontaneous or caffeine-induced Ca(2+) sparks...
  49. ncbi Central domain of the human cardiac muscle ryanodine receptor does not mediate interaction with FKBP12.6
    Spyros Zissimopoulos
    Wales Heart Research Institute, Department of Cardiology, Wales College of Medicine, Cardiff University, UK
    Cell Biochem Biophys 43:203-19. 2005
    ..The cardiac muscle RyR isoform (RyR2) specifically associates with a distinct FKBP isoform, FKBP12.6...
  50. ncbi Assessment of sarcoplasmic reticulum Ca(2+) flux pathways in cardiomyocytes from rabbits with infarct-induced left-ventricular dysfunction
    Paul Neary
    Department of Medical Cardiology, Glasgow Royal Infirmary, Glasgow G31 2ER, UK
    Pflugers Arch 444:360-71. 2002
    ..with sarco-endoplasmic reticulum Ca(2+) ATPase type 2 (SERCA2)-mediated uptake, ryanodine receptor type 2 (RyR2)-mediated Ca(2+) efflux and background SR Ca(2+) leak were measured in suspensions of permeabilised myocytes...
  51. pmc Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor
    Huihui Kong
    Department of Physiology and Biophysics, Libin Cardiovascular Institute of Alberta, 3330 Hospital Drive N W, University of Calgary, Calgary, AB, Canada
    Biochem J 414:441-52. 2008
    ..present study, we investigated the effects of caffeine on spontaneous Ca(2+) release and on the response of single RyR2 (cardiac RyR) channels to luminal or cytosolic Ca(2+)...
  52. pmc Bioinformatic mapping and production of recombinant N-terminal domains of human cardiac ryanodine receptor 2
    Vladena Bauerová-Hlinková
    Department of Protein Structure and Function, Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska cesta 21, 845 51 Bratislava, Slovakia
    Protein Expr Purif 71:33-41. 2010
    ..with catecholaminergic polymorphic ventricular tachycardia (CPVT1) and arrhythmogenic right ventricular dysplasia (ARVD2)...
  53. pmc Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy
    Prince J Kannankeril
    Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 103:12179-84. 2006
    Mutations in the cardiac ryanodine receptor 2 (RyR2) have been associated with catecholaminergic polymorphic ventricular tachycardia and a form of arrhythmogenic right ventricular dysplasia...
  54. ncbi Selective down-regulation of sub-endocardial ryanodine receptor expression in a rabbit model of left ventricular dysfunction
    Susan Currie
    Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
    J Mol Cell Cardiol 39:309-17. 2005
    ..the normal and diseased heart, left ventricular transmural expression and activity of the ryanodine receptor (RyR2) was studied in a rabbit coronary artery ligation model of left ventricular dysfunction (LVD)...
  55. pmc Functional groups of ryanodine receptors in rat ventricular cells
    V Lukyanenko
    Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 W Lombard St, Room S213, Baltimore, MD 21201, USA
    J Physiol 583:251-69. 2007
    ..g. circular waves and Ca2+ sparks in perinuclear area) raised questions about the classical views of RyR2 distribution and organization within ventricular cells...
  56. pmc Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass
    Fredrick A Hilliard
    Division of Clinical Pharmacology, Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, Nashville, TN 37232 0575, USA
    J Mol Cell Cardiol 48:293-301. 2010
    ..polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin...
  57. ncbi [Effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins in rabbits with heart failure]
    Yu Liu
    Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
    Zhonghua Xin Xue Guan Bing Za Zhi 37:883-6. 2009
    ..To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF)...
  58. pmc Amitriptyline activates cardiac ryanodine channels and causes spontaneous sarcoplasmic reticulum calcium release
    Nagesh Chopra
    Oates Institute for Experimental Therapeutics and Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 0575, USA
    Mol Pharmacol 75:183-95. 2009
    ..Here, we hypothesize that AMT activates cardiac ryanodine channels (RyR2), causing premature Ca(2+) release from the sarcoplasmic reticulum (SR), a mechanism identified by genetic studies ..
  59. ncbi [Effect of carvedilol and perindopril on Ca(2+) pump activity and Ca(2+)-release channel density in myocardial sarcoplasmic reticulum in rats with chronic heart failure following myocardial infarction]
    Zhao Hua Geng
    Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China
    Nan Fang Yi Ke Da Xue Xue Bao 29:1461-4. 2009
    ..combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction.
  60. ncbi Exercise and tachycardia increase NADPH oxidase and ryanodine receptor-2 activity: possible role in cardioprotection
    Gina Sanchez
    Programa de Fisiopatología, Instituto de Ciencias Biomédicas y Centro FONDAP de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, Chile
    Cardiovasc Res 77:380-6. 2008
    Our objective was to investigate in cardiac muscle the contribution of NADPH oxidase to (a) ryanodine receptor-2 (RyR2) S-glutathionylation and (b) the preconditioning effects of exercise and tachycardia on infarct size following coronary ..
  61. ncbi Streptozotocin-induced diabetes increases disulfide bond formation on cardiac ryanodine receptor (RyR2)
    Keshore R Bidasee
    Department of Pharmacology, University of Nebraska Medical Center, 986260 Nebraska Medical Center, Omaha, NE 68198 6260, USA
    J Pharmacol Exp Ther 305:989-98. 2003
    In a previous study, we showed that after 6 weeks of streptozotocin-induced diabetes (6D), expression of type 2 ryanodine receptor calcium-release channels (RyR2) did not change significantly in rat hearts...
  62. pmc Calcium/calmodulin-dependent protein kinase IIdelta associates with the ryanodine receptor complex and regulates channel function in rabbit heart
    Susan Currie
    Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK
    Biochem J 377:357-66. 2004
    ..study examined the association of endogenous CaMKII (calcium/calmodulin-dependent protein kinase II) with the RyR2 complex and whether this enzyme could modulate RyR2 function in isolated rabbit ventricular myocardium...
  63. pmc Luminal Ca2+ regulation of single cardiac ryanodine receptors: insights provided by calsequestrin and its mutants
    Jia Qin
    Department of Molecular Physiology and Biophysics, Rush University Medical Center, Chicago, IL 60612, USA
    J Gen Physiol 131:325-34. 2008
    The luminal Ca2+ regulation of cardiac ryanodine receptor (RyR2) was explored at the single channel level. The luminal Ca2+ and Mg2+ sensitivity of single CSQ2-stripped and CSQ2-associated RyR2 channels was defined...
  64. doi Conditional FKBP12.6 overexpression in mouse cardiac myocytes prevents triggered ventricular tachycardia through specific alterations in excitation-contraction coupling
    Barnabas Gellen
    INSERM, U698, Paris, France
    Circulation 117:1778-86. 2008
    Ca(2+) release from the sarcoplasmic reticulum via the ryanodine receptor (RyR2) activates cardiac myocyte contraction. An important regulator of RyR2 function is FKBP12.6, which stabilizes RyR2 in the closed state during diastole...
  65. pmc Sudden infant death syndrome in mice with an inherited mutation in RyR2
    Nitin Mathur
    Department of Molecular Physiology and Biophysics, Division of Cardiology, Baylor College of Medicine, Houston, TX 77030, USA
    Circ Arrhythm Electrophysiol 2:677-85. 2009
    Mutations in the cardiac ryanodine receptor gene (RyR2) have been recently identified in victims of sudden infant death syndrome...
  66. pmc Protein protein interactions between triadin and calsequestrin are involved in modulation of sarcoplasmic reticulum calcium release in cardiac myocytes
    Dmitry Terentyev
    Department of Physiology and Cell Biology, 505 Davis Heart and Lung Research Institute, The Ohio State University, 473 W 12th Ave, Columbus, OH 43210, USA
    J Physiol 583:71-80. 2007
    ..In cardiac muscle, intracellular Ca2+ release is controlled by a number of proteins including the ryanodine receptor (RyR2), calsequestrin (CASQ2), triadin-1 (Trd) and junctin (Jn) which form a complex in the junctional sarcoplasmic ..
  67. pmc Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing catecholaminergic polymorphic ventricular tachycardia
    Lei Song
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    J Clin Invest 117:1814-23. 2007
    ..polymorphic ventricular tachycardia (CPVT) is a familial disorder caused by cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) gene mutations...
  68. doi Differential alterations in expressions of ryanodine receptor subtypes in cerebellar cortical neurons of an ataxic mutant, rolling mouse Nagoya
    K Sawada
    Department of Anatomy and Developmental Neurobiology, University of Tokushima Graduate School Institute of Health Biosciences, 3 18 15 Kuramoto cho, Tokushima 770 8503, Japan
    Neuroscience 152:609-17. 2008
    This study aimed to clarify changes in the spatial expressions of types 1, 2 and 3 ryanodine receptors (RyR1, RyR2 and RyR3) in the cerebellum of a Ca(2+) channel alpha(1A) subunit mutant, rolling mouse Nagoya...
  69. pmc Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation
    Chun Hong Shao
    Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
    J Appl Physiol (1985) 106:1280-92. 2009
    ..Steady-state type 2 ryanodine receptor (RyR2) protein did not change, but its response to Ca(2+) was altered. RyR2 also exhibited 1.8- and 1...
  70. pmc Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor
    Shigeki Kobayashi
    Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
    J Am Coll Cardiol 53:1993-2005. 2009
    ..We sought to investigate the effect of dantrolene, a drug generally used to treat malignant hyperthermia, on the Ca2+ release and cardiomyocyte function in failing hearts...
  71. pmc Ryanodine receptor luminal Ca2+ regulation: swapping calsequestrin and channel isoforms
    Jia Qin
    Department of Molecular Biophysics and Physiology, Rush University Medical Center, Chicago, Illinois, USA
    Biophys J 97:1961-70. 2009
    ..Here, CSQ-dependent luminal Ca(2+) regulation of skeletal (RyR1) and cardiac (RyR2) channels is explored...
  72. ncbi Triadin overexpression stimulates excitation-contraction coupling and increases predisposition to cellular arrhythmia in cardiac myocytes
    Dmitry Terentyev
    Department of Physiology and Cell Biology, Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA
    Circ Res 96:651-8. 2005
    Triadin 1 (TRD) is an integral membrane protein that associates with the ryanodine receptor (RyR2), calsequestrin (CASQ2) and junctin to form a macromolecular Ca signaling complex in the cardiac junctional sarcoplasmic reticulum (SR)...
  73. ncbi Functional interaction of neuronal Cav1.3 L-type calcium channel with ryanodine receptor type 2 in the rat hippocampus
    Sunoh Kim
    Life Sciences Division, Korea Institute of Science and Technology, 39 1 Hawholgok dong, Sungbuk Gu, Seoul, Korea
    J Biol Chem 282:32877-89. 2007
    ..3 alpha(1) subunit interacts with a partial N-terminal amino acid sequence of ryanodine receptor type 2 (RyR2). Reverse transcription-PCR and Western blot assays revealed high expression of both Ca(v)1...
  74. ncbi Modulation of ryanodine receptor by luminal calcium and accessory proteins in health and cardiac disease
    Sandor Gyorke
    Department of Physiology and Cell Biology, 505 Davis Heart and Lung Research Institute, The Ohio State University, 473 West 12th Avenue, Columbus, OH 43210, USA
    Cardiovasc Res 77:245-55. 2008
    The cardiac ryanodine receptor (RyR2) is the sarcoplasmic reticulum (SR) Ca(2+) release channel which is responsible for generation of the cytosolic Ca(2+) transient required for activation of cardiac contraction...
  75. pmc Subtype identification and functional characterization of ryanodine receptors in rat cerebral artery myocytes
    Thirumalini Vaithianathan
    Department Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
    Am J Physiol Cell Physiol 299:C264-78. 2010
    ..05-5 microM), and unaffected by heparin (2 mg/ml). This phenotype resembles that of cardiac RyR and recombinant RyR2. RT-PCR detected RyR1, RyR2, and RyR3 transcripts in cerebral artery myocytes...
  76. pmc Intra-sarcoplasmic reticulum Ca2+ oscillations are driven by dynamic regulation of ryanodine receptor function by luminal Ca2+ in cardiomyocytes
    Sarah C W Stevens
    Department of Physiology and Cell Biology, Ohio State University, Columbus, OH 43214, USA
    J Physiol 587:4863-72. 2009
    During the cardiac cycle, the release of Ca(2+) from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR2) channel complex is controlled by the levels of cytosolic and luminal Ca(2+) and alterations in these regulatory ..
  77. pmc Intracellular translocation of calmodulin and Ca2+/calmodulin-dependent protein kinase II during the development of hypertrophy in neonatal cardiomyocytes
    Jaya Pal Gangopadhyay
    Boston Biomedical Research Institute, Watertown, MA 02472, USA
    Biochem Biophys Res Commun 396:515-21. 2010
    ..cardiomyocytes with endothelin-1 (ET-1) first produces conformational disorder within the ryanodine receptor (RyR2) and diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR), then develops hypertrophy (HT) in the ..
  78. pmc RYR2 proteins contribute to the formation of Ca(2+) sparks in smooth muscle
    Guangju Ji
    Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853 6401, USA
    J Gen Physiol 123:377-86. 2004
    ..FKBP12.6 proteins interact with RYR2 Ca(2+) release channels and the absence of these proteins predictably alters the amplitude and kinetics of RYR2 ..
  79. ncbi Three-dimensional reconstruction of the recombinant type 2 ryanodine receptor and localization of its divergent region 1
    Zheng Liu
    Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA
    J Biol Chem 277:46712-9. 2002
    Isoform 2 of the ryanodine receptor (RyR2) is the major calcium release channel in cardiac muscle...
  80. ncbi Differential expression of the cardiac ryanodine receptor in normal and arrhythmogenic right ventricular cardiomyopathy canine hearts
    Kathryn M Meurs
    Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA
    Hum Genet 120:111-8. 2006
    ..the cardiac ryanodine receptor (RyR2) gene have been identified in some human families with a unique form of ARVC, ARVC2. Although the RyR2 has significant importance in excitation-contraction coupling across the ventricles, mutations ..
  81. ncbi Mg2+ activates the ryanodine receptor type 2 (RyR2) at intermediate Ca2+ concentrations
    Akihito Chugun
    Department of Pharmacology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    Am J Physiol Cell Physiol 292:C535-44. 2007
    To clarify whether activity of the ryanodine receptor type 2 (RyR2) is reduced in the sarcoplasmic reticulum (SR) of cardiac muscle, as is the case with the ryanodine receptor type 1 (RyR1), Ca(2+)-dependent [(3)H]ryanodine binding, a ..
  82. doi Identification of target domains of the cardiac ryanodine receptor to correct channel disorder in failing hearts
    Takeshi Yamamoto
    Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1 1 1 Minamikogushi, Ube, Yamaguchi, 755 8505, Japan
    Circulation 117:762-72. 2008
    ..that defective interdomain interaction between N-terminal (0 to 600) and central regions (2000 to 2500) of ryanodine receptor 2 (RyR2) induces Ca2+ leak in failing hearts and that K201 (JTV519) inhibits the Ca2+ leak by correcting the ..
  83. pmc Luminal Mg2+, a key factor controlling RYR2-mediated Ca2+ release: cytoplasmic and luminal regulation modeled in a tetrameric channel
    Derek R Laver
    School of Biomedical Sciences, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308, Australia
    J Gen Physiol 132:429-46. 2008
    ..The effects of luminal Ca(2+) and Mg(2+) on sheep RYR2 were measured in lipid bilayers...
  84. pmc Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S-nitrosylation
    Honglan Wang
    Department of Physiology and Cell Biology, Ohio State University, 1645 Neil Avenue, Columbus, OH 43210, USA
    J Physiol 588:2905-17. 2010
    The sarcoplasmic reticulum (SR) Ca(2+) release channel (ryanodine receptor, RyR2) has been proposed to be an end target of neuronal nitric oxide synthase (NOS1) signalling...
  85. ncbi Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization
    M G Mattei
    Unité INSERM 242, Hopital d Enfants de la Timone, Marseille, France
    Genomics 22:202-4. 1994
    ..the location on murine chromosomes of the three genes of the ryanodine receptor/Ca2+ channel family: RYR1, RYR2, and RYR3...
  86. ncbi Regulation of tissue-specific expression of the skeletal muscle ryanodine receptor gene
    S Schmoelzl
    Institute of Veterinary Medicine, University of Gottingen, 37073 Gottingen, Federal Republic of Germany
    J Biol Chem 271:4763-9. 1996
    ..Three genes, i. e. ryr1, ryr2, and ryr3, have been identified coding for a skeletal muscle, cardiac muscle, and brain isoform, respectively...
  87. ncbi Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-sensitive calcium stores
    C Martin
    Department of Biochemistry, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom
    Am J Physiol 277:C243-52. 1999
    ..mRNAs in the myometrium: ryr3 mRNA is the predominant subtype, with much lower levels of expression for ryr1 and ryr2 mRNAs, suggesting that the ryanodine Ca(2+) release mechanism in rat myometrium is largely encoded by ryr3...
  88. ncbi Calcium handling proteins in isolated spinal motoneurons
    L van den Bosch
    Laboratory of Neurobiology, University of Leuven, Belgium
    Life Sci 65:1597-606. 1999
    ..The inositol 1,4,5-trisphosphate receptor (IP3R) mRNAs were mainly transcribed from the IP3RI and IP3RII genes. Heterogeneity was also observed for the ryanodine receptors (RyR) as the RyR1, RyR2 and RyR3 mRNAs were present.
  89. ncbi Tectoridins modulate skeletal and cardiac muscle sarcoplasmic reticulum calcium-release channels
    K R Bidasee
    Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis 46202 5120, USA
    J Pharmacol Exp Ther 293:1074-83. 2000
    ..2 +/- 0.4 nM (K(d) = 2.4 nM). TTR demonstrated a 3-fold higher affinity for cardiac RyR (RyR2) [IC(50) value of 5.2 +/- 0.6 microM (K(d) = 0.95 +/- 0.3 microM)] than for RyR1...
  90. ncbi Smooth muscle tissues express a major dominant negative splice variant of the type 3 Ca2+ release channel (ryanodine receptor)
    Dawei Jiang
    Cardiovascular Research Group, Department of Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 278:4763-9. 2003
    ..RyR3 splice variant was also able to form heteromeric channels with and suppress the activity of the type 2 ryanodine receptor (RyR2)...
  91. pmc Advancing age alters the expression of the ryanodine receptor 3 isoform in adult rat superior cervical ganglia
    Conwin K Vanterpool
    Dept of Physiology and Pharmacology, Loma Linda Univ, School of Medicine, Loma Linda, CA 92350, USA
    J Appl Physiol (1985) 101:392-400. 2006
    ..Surprisingly, ryr1 expression was undetectable in all age groups and ryr2 and ryr3 are the predominantly transcribed isoforms in the adult rat SCG...
  92. pmc Ca2+/calmodulin kinase II increases ryanodine binding and Ca2+-induced sarcoplasmic reticulum Ca2+ release kinetics during beta-adrenergic stimulation
    Paola Ferrero
    Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, 60 y 120, 1900 La Plata, Argentina
    J Mol Cell Cardiol 43:281-91. 2007
    ..of both PKA and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) cascades to the phosphorylation of RyR2 and the activity of the channel during beta-adrenergic receptor (betaAR) stimulation...
  93. pmc HIV-1 Tat activates neuronal ryanodine receptors with rapid induction of the unfolded protein response and mitochondrial hyperpolarization
    John P Norman
    Center for Neural Development and Disease, The University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    PLoS ONE 3:e3731. 2008
    ..In this report, we demonstrate that Tat induces rapid loss of ER calcium mediated by the ryanodine receptor (RyR), followed by the unfolded protein response (UPR) and pathologic dilatation of the ER in cortical neurons in vitro...
  94. pmc The signalling pathway of CaMKII-mediated apoptosis and necrosis in the ischemia/reperfusion injury
    Margarita A Salas
    Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, 60 y 120, 1900 La Plata, Argentina
    J Mol Cell Cardiol 48:1298-306. 2010
    ..Instead, there was a proportional decrease in the phosphorylation of Ser2815 site of ryanodine receptors (RyR2) and the amount of RyR2 at the onset of reperfusion, i.e. the ratio Ser2815/RyR2 did not change...
  95. doi Cardiomyocytes hypertrophic status after myocardial infarction determines distinct types of arrhythmia: role of the ryanodine receptor
    Jeremy Fauconnier
    Inserm U637, Université Montpellier1, Department of Cardiovascular Physiopathology, 371 Avenue du Doyen Gaston Giraud, F34295 Montpellier Cedex 5, France
    Prog Biophys Mol Biol 103:71-80. 2010
    ..The occurrence of spontaneous Ca(2+) sparks, reflecting ryanodine receptor (RyR2) diastolic activity, increased with hypertrophy...
  96. doi Diabetes-related defects in sarcoplasmic Ca2+ release are prevented by inactivation of G(alpha)11 and G(alpha)q in murine cardiomyocytes
    Dieter Paul Hoyer
    Department of Internal Medicine III, University of Cologne, Kerpener Str 62, 50937 Cologne, Germany
    Mol Cell Biochem 341:235-44. 2010
    ..tested in vitro based on a (45)Ca(2+) assay and protein densities as well as gene expression of ryanodine receptor (RyR2), FKBP12.6, sorcin, and annexin A7 were analyzed by immunoblot and RT-PCR...
  97. pmc Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks
    Tao Guo
    Department of Pharmacology, University of California, Davis, 451 Health Science Dr, Davis, CA 95616, USA
    Circ Res 106:1743-52. 2010
    FK506-binding proteins FKBP12.6 and FKBP12 are associated with cardiac ryanodine receptors (RyR2), and cAMP-dependent protein kinase A (PKA)-dependent phosphorylation of RyR2 was proposed to interrupt FKBP12...
  98. pmc Novel carvedilol analogues that suppress store-overload-induced Ca2+ release
    Chris D Smith
    Department of Chemistry, University of Calgary, Calgary, Alberta T2N 1N4, Canada
    J Med Chem 56:8626-55. 2013
    ..activity is in part because of its ability to inhibit store-overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization, and bioassay of ca...
  99. doi A comparative study indicates both positive and purifying selection within ryanodine receptor (RyR) genes, as well as correlated evolution
    Patrick B McKay
    Department of Integrative Biology, University of Guelph, Ontario, Canada
    J Exp Zool A Ecol Genet Physiol 321:151-63. 2014
    ..RyRs form a small gene family and vertebrates have three major isoforms, RyR1, RyR2, and RyR3, which are mixed and matched in different combinations in different tissues resulting in different Ca(2+) ..
  100. doi TGFβ1 downregulates neurite outgrowth, expression of Ca2+ transporters, and mitochondrial dynamics of in vitro cerebellar granule cells
    Katarina Jaskova
    aInstitute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia bDepartment of Pharmacology, Faculty of Medicine, University of Tartu, Tartu, Estonia
    Neuroreport 25:340-6. 2014
    ..the gene expression of additional intracellular Ca transporters such as IP3R2, ryanodine receptor type 1 (RyR1), RyR2, and SERCA2...
  101. pmc Role of RyR2 phosphorylation in heart failure and arrhythmias: protein kinase A-mediated hyperphosphorylation of the ryanodine receptor at serine 2808 does not alter cardiac contractility or cause heart failure and arrhythmias
    Steven R Houser
    From the Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA
    Circ Res 114:1320-7; discussion 1327. 2014
    ..article discusses the hypothesis that protein kinase A (PKA)-mediated phosphorylation of the Ryanodine Receptor (RyR) at a single serine (RyRS2808) is essential for normal sympathetic regulation of cardiac myocyte contractility and ..

Research Grants62

  1. RAZVAN LIVIU CORNEA; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): Mutation and dysregulation of the cardiac ryanodine receptor (RyR2) or sarcoplasmic reticulum (SR) calcium release channel contributes directly to catecholaminergic polymorphic ventricular tachycardia ..
  2. Michael Fill; Fiscal Year: 2016
    ..cardiac muscle, triggered (by surface Ca2+ influx) or spontaneous opening of multiple type-2 ryanodine receptors (RyR2) at discrete sarcoplasmic reticulum (SR) generates localized elemental Ca2+ release events called Ca2+ sparks...
  3. Sandor Gyorke; Fiscal Year: 2016
    ..On a beat-to-beat basis, intracellular Ca release through sarcoplasmic reticulum (SR) cardiac ryanodine receptor (RyR2) channels is elicited by Ca entry through sarcolemmal voltage-gated Ca channels, a process known as Ca-induced Ca ..
  4. Isoform-Specific Regulation of Skeletal Muscle Calcium Channel by Calmodulin
    Naohiro Yamaguchi; Fiscal Year: 2013
    ..RyR1 is activated, whereas RyR2 (cardiac muscle isoform) is inhibited by CaM at submicromolar Ca2+ concentrations...
  5. Sandor Gyorke; Fiscal Year: 2016
    ..Altered Ca release from the sarcoplasmic reticulum (SR) due to deregulated cardiac ryanodine receptor (RyR2) function (i.e...
  6. ALLOSTERIC SITE STRUCTURES OF CARDIOVASCULAR CHANNELS
    Arthur Karlin; Fiscal Year: 2011
    The cardiac ryanodine receptor calcium-release channel (RyR2) and the smooth-muscle large-conductance calcium-and-voltage-activated potassium (BK) channel are vital participants in normal and pathological cardiovascular physiology...
  7. WILLIAM JONATHAN LEDERER; Fiscal Year: 2014
    ..control ventricular myocytes;2. ventricular myocytes in which RyR2 properties have been altered;3. ventricular myocytes when microtubules are modulated;4...
  8. Structural Basis of Dysfunctional Calcium Release Channels in Heart Disease
    Zheng Liu; Fiscal Year: 2013
    ..provided by applicant): There is a fundamental gap in understanding how dysfunction of cardiac ryanodine receptor (RyR2) leads to certain type of sudden cardiac death and heart failure...
  9. RAIMOND LESTER WINSLOW; Fiscal Year: 2015
    ..We will examine how mutations in the calcium release channel (ryanodine receptor type 2, RyR2) and the Ca2+ binding protein, calsequestrin (CASQ2) contribute to Ca2+ dependent arrhythmogenesis...
  10. Function and regulation of elemental Ca2+ signaling in urethral smooth muscle
    Ronghua Zhuge; Fiscal Year: 2013
    ..short-lived Ca2+ transients ("Ca2+ sparks") that result from the spontaneous opening of type 2 ryanodine receptors (RyR2) in the sarcoplasmic reticulum, and their ion channel targets in the plasma membrane in urethral smooth muscle (USM)..
  11. Xander H T Wehrens; Fiscal Year: 2016
    PROJECT SUMMARY/ ABSTRACT Ryanodine receptors (RyR2) regulate intracellular Ca2+ release from the sarcoplasmic reticulum (SR), and are important determinants of cardiac contractility...
  12. Bjorn C Knollmann; Fiscal Year: 2015
    ..Experimental data from a RyR2 mutant mouse model and theoretical considerations favor the Purkinje network...
  13. Local Calcium Signaling in Pulmonary Arteries
    JAMES SK SHAM; Fiscal Year: 2012
    ..Our recent study shows that all three RyR subtypes, RyR1, RyR2 and RyR3, are expressed in PASMCs;and these specific RyR-gated Ca2+ stores are distributed heterogeneously in ..
  14. Hector H Valdivia; Fiscal Year: 2016
    ..The vast majority of CPVT mutations have been localized to three loci ("hot spots") of the RyR2 protein that affect different aspects of RyR function, however, the molecular mechanism that links a mutation in ..
  15. Muscle: Excitation/Contraction Coupling Gordon Research Conference
    Paul D Allen; Fiscal Year: 2011
    ..5. Timothy syndrome (Cardiac DHPR). and 5. catecholaminergic polymorphic ventricular tachycardia (RyR2 and Calsequestrin 2)...
  16. Role of CaMKII Phosphorylation of RyR in Pathological &Physiological Hypertrophy
    Jonathan L Respress; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Ryanodine receptors (RyR2) regulate intracellular Ca2+ release from the sarcoplasmic reticulum (SR), and are important determinants of cardiac contractility...
  17. Ryanodine receptor in cardiac hypertrophy and heart failure
    GERHARD W MEISSNER; Fiscal Year: 2013
    The goal of our proposed research is to understand how the cardiac Ca2+ release channel (ryanodine receptor, RyR2) regulates cardiac function...
  18. James B Martins; Fiscal Year: 2014
    ..After activation mapping, tissue at the mechanistic origin of VTVF will be excised for measurements of ROS, CaMKII, RyR2, phospholamban, SERCA2a, and NCX and in vitro microelectrode testing...
  19. Alan V Smrcka; Fiscal Year: 2016
    ..will achieve these goals by exploring the following hypotheses: 1) Scaffolding to the Type II Ryanodine receptor (RyR2) and muscle A kinase anchoring protein (mAKAP) specifies distinct compartmentation of PLCe in cardiac cells...
  20. Fibrillation and Defibrillation
    Peng Sheng Chen; Fiscal Year: 2010
    ..They also found that carvedilol and its analog (VK-II-36) can effectively reduce the sensitivity of type 2 ryanodine receptor (RyR2) to luminal Ca and suppress SR Ca release in rat ventricular myocytes...
  21. Molecular basis of Ca2+ leak in heart
    GEORGE BLAIR WILLIAMS; Fiscal Year: 2013
    ..from control mice (C57BL/6) and from mutant mice with specific alterations in the cardiac ryanodine receptor (RyR2) (C57BL/6- R2474S) that produce Ca2+-dependent arrhythmias (see [1])...
  22. Isaac N Pessah; Fiscal Year: 2016
    ..Determine whether heritable mutations in ryr1 and ryr2 that increase sensitivity to halogenated compounds in the human population increase susceptibility to PCB ..
  23. ANDREW ROBERT MARKS; Fiscal Year: 2016
    ..This project focuses on elucidating defects in the regulation of type 2 ryanodine receptor (RyR2)/Ca2+ release channel, which is required for cardiac excitation-contraction (EC) coupling...
  24. ANDREW ROBERT MARKS; Fiscal Year: 2014
    ..The applicant proposes to test the hypothesis that "leaky" RyR1 and RyR2 channels due to hypernitrosylation of the channels are a common feature of MDs that involve disruption of the DCG...
  25. Yibin Wang; Fiscal Year: 2015
    ..PP2Ce has specific activity towards p-PLN without significant impact on p-RyR2. PP2Ce protein has a rapid turn- over rate and its expression is significantly induced by prolonged 2AR stimulation ..
  26. ANDREW ROBERT MARKS; Fiscal Year: 2014
    ..The applicant proposes to determine the mechanism underlying leaky RyR2 channels in atrial and pulmonary vein myocytes in animal models of AF, and test a novel drug S107 (a rycal), ..
  27. Calcium Triggered Arrhythmias and Sudden Cardiac Arrest
    Richard L Moss; Fiscal Year: 2013
    ..Subproject 1 will determine the functional consequences of novel RYR2 mutations, including a common polymorphism in RyR2, and the mechanisms by which the molecular phenotype causes the ..
  28. S MURTHY KARNAM; Fiscal Year: 2016
    ..initiated by cPLA2-dependent Ca2+ influx leading to Ca2+- and cyclic ADP ribose-induced Ca2+ release via ryanodine (RYR2) receptors...
  29. Isaac N Pessah; Fiscal Year: 2014
    ..The molecular mechanisms responsible for enantiospecific activation of RyR1 and RyR2 channel complexes will be investigated using biochemical, biophysical and cellular analyses...
  30. Rational Design of New Drugs to Treat Ventricular Arrhythmias
    Jonathan J Abramson; Fiscal Year: 2012
    ..Given the prominent role of RyR2 in the control of Ca2+ homeostasis, pharmacological strategies to modulate RyR2 stability and gating have shown ..
  31. Molecular Basis and Treatment of Cardiac Arrhythmias
    SUI RONG WAYNE CHEN; Fiscal Year: 2013
    ..SOICR activity and DAD-associated ventricular arrhythmias are common in HF and in cardiac ryanodine receptor (RyR2)-associated ventricular arrhythmias...
  32. ANESTHETIC REACTIONS IN SURGERY
    David Thomas; Fiscal Year: 2003
    ..125I]CaM binding properties of the different channel isoforms (RYR1, RYR2, and RYR3) will be characterized, and compared with CaM's functional effects on the isolated channels as determined ..
  33. Molecular Mechanisms of Ventricular Fibrillation
    JOSE JALIFE; Fiscal Year: 2007
    ..have been reported in individuals affected by CPVT and arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2). Our central objective is to determine the electrophysiological mechanisms of CPVT...
  34. Coupled gating between intracellular calcium release ch*
    Andrew Marks; Fiscal Year: 2004
    ..Significant new findings and preliminary data include: 1) FKBP12/12.6 stabilize RyR1 and RyR2 function; 2) identification of the binding site for FKBP12/12...
  35. Calmodulin regulation of SR calcium release channels
    Bradley Fruen; Fiscal Year: 2007
    ..the molecular mechanisms that control the RYR isoforms expressed in skeletal muscle (RYR1) and cardiac muscle (RYR2)...
  36. FKBP12/RYR MECHANISMS UNDERLYING PCB EFFECTS OF LEARNING
    Isaac Pessah; Fiscal Year: 2000
    ..Preliminary work has revealed that PCB170 is one of the most potent modulators of the ryanodine receptor (RyR2)/immunophilin (FKBP12) Ca2+ channel complex which predominates within hippocampal neurons...
  37. Anthracycline cardiotoxicity and calsequestrin function
    SUSAN SHADLE; Fiscal Year: 2002
    ..using Ca-45 competitive binding assays; 4) to determine the conformation of the cardiac ryanodine receptor (RyR2) in isolated SR vesicles after preincubation with anthracyclines; ryanodine binding assays will be used...
  38. Molecular Characterization of Dantrolene Binding Site
    Jerome Parness; Fiscal Year: 2007
    ..Dantrolene appears to interact with RyR1 rather than cardiac RyR2 despite an identical DP1 sequence...
  39. Genetic Determinants of Sudden Cardiac Death
    Christine Albert; Fiscal Year: 2006
    ..Mutations in cardiac ion channel genes including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2 have been implicated in monogenic traits with a high risk of SCD, such as the Iong-QT, Brugada, sudden infant death ..
  40. CALCIUM SPARKS IN HEART MUSCLE
    WILLIAM LEDERER; Fiscal Year: 2007
    ..How does RyR2 behavior influence the triggering of Ca2+ sparks? 3. How does membrane potential influence Ca2+ spark triggering? 4...
  41. Regulation of cardiac ion channel function via allosteric modulators
    Andrew Marks; Fiscal Year: 2007
    ..6 (calstabin1/2). Four aims are proposed: Aim 1: Allosteric regulation of RyR2 by small molecules that enhance binding of calstabin2 to RyR2...
  42. CARDIAC AND SKELETAL MUSCLE CALCIUM RELEASE CHANNELS
    Andrew Marks; Fiscal Year: 2009
    ..Our preliminary data suggest that the effect of PKA phosphorylation of RyR2 on FKBP12.6 binding is mediated by electrostatic repulsion due to negative charges on FKBP12...
  43. RYANODINE RECEPTOR DYSFUNCTION IN DIABETIC HEARTS
    Keshore Bidasee; Fiscal Year: 2002
    Applicant's Abstract Release of calcium ions from the sarcoplasmic reticulum via type 2 ryanodine receptors (RyR2) is an integral step in the cascade of events leading to cardiac muscle contraction...
  44. Role of Ryanodine Receptors in Diabetic Cadiomyopathy
    Keshore R Bidasee; Fiscal Year: 2010
    ..One of the proteins that contribute to this defect is type 2 ryanodine receptor (RyR2), the channel through which Ca2+ leave the sarcoplasmic reticulum to effect contraction...
  45. REGULATION OF SARCOPLASMIC RETICULUM CA2+ RELEASE
    Gerhard Meissner; Fiscal Year: 2009
    ..The RyR ion channels are composed of four RyR 560 kDa peptide subunits and various associated proteins with a total ..
  46. Gene Targets of NKX 2.5 in the Conduction System
    Melvin Scheinman; Fiscal Year: 2004
    ..MinK and HCN-1) in the pathogenesis of arrhythmias in the ventricular restricted knockout mouse model. This will be done by using in-situ hybridization and immunohistochemistry to follow the pattern of expression of these ion channels. ..
  47. Cardiac Arrhythmia Mechanisms
    JOSE JALIFE; Fiscal Year: 2005
    ....
  48. Heterogeneity of hypoxic Ca2+ release in pulmonary and *
    Yong Xiao Wang; Fiscal Year: 2006
    ..Our preliminary studies, together with previous findings, suggest that specific RyR subtypes (RyR1, RyR2 and RyR3) are differentially expressed in the vasculature...
  49. Store-Operated Calcium Entry and Apoptosis
    Jianjie Ma; Fiscal Year: 2010
    ..Knowledge on the molecular interactions between apoptosis mediators and cytosolic factors that control SOCE will enable us to establish therapeutic agents that target Ca signaling in cancer and degenerative diseases. ..
  50. Mechanisms for hypoxic Ca2+ release in pulmonary artery myocytes
    Yong Xiao Wang; Fiscal Year: 2010
    ..The findings from this proposal will enhance our understanding of cellular molecular mechanisms for hypoxic [Ca2+]i rise in PASMCs and associated HPV, and may lead to identify potential novel targets to treat pulmonary hypertension. ..
  51. Biomarkers of Ventricular and Vascular Remodeling
    Vasan Ramachandran; Fiscal Year: 2009
    ..Our proposal will advance understanding of the role of vascular growth factors in initiating and promoting vascular stiffness, LV dysfunction and HTN. ..
  52. Ethanol Effects of SR Ca2+ Release in Cardiac Myocytes
    J Wasserstrom; Fiscal Year: 2005
    ....
  53. Novel Signaling for Ca2+ and Release in Airway Myocytes
    Yong Xiao Wang; Fiscal Year: 2007
    ..This novel signaling pathway, ADP-ribosyl cyclase-cADPR-FKBP12.6-RyR, may be hyper-functioned in asthma, contributing to the airway muscle Ca2+ and contractile hyperresponsiveness to ..
  54. Neuroprotection and Promotion of Repair Following Neurotoxic Injury
    Isaac Pessah; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  55. Genetics of Oxidative Stress in Ventricular Remodeling
    Vasan Ramachandran; Fiscal Year: 2003
    ....
  56. Ventricular Matrix Remodeling: Correlates and Prognosis
    Vasan Ramachandran; Fiscal Year: 2004
    ..The proposed translational research will likely yield seminal information that could directly improve our efforts to prevent CHF through the biochemical assessment of cardiac ECM remodeling. ..
  57. Aldosterone in Vascular Remodeling and Dysfunction
    Vasan Ramachandran; Fiscal Year: 2008
    ..Activities for career development of the candidate are also planned in the areas of proteomics and genetic epidemiology. ..
  58. Annual Autism, Genes and the Environment Conference
    Isaac Pessah; Fiscal Year: 2004
    ..Three workshops for parents and caregivers will address the following: Dietary Factors Influencing Autistic Behaviors; Pharmacological Interventions, and Behavioral Interventions. ..
  59. NOVEL CELLULAR MECHANISMS IN CORTEX DEVELOPMENT
    Paul Worley; Fiscal Year: 2004
    ..Planned activities make full use of the outstanding opportunities for collaboration and career development at Johns Hopkins School of Medicine. ..
  60. Cardiac Interactions of New Adriamycin Analogs and Taxol
    Richard Olson; Fiscal Year: 2004
    ....
  61. FUNCTIONAL RESPONSES OF EXTRAOCULAR EYE MUSCLES TO T3
    Neal Rubinstein; Fiscal Year: 2005
    ..abstract_text> ..
  62. Role of MG29 in E-C Coupling of Striated Muscles
    Jianjie Ma; Fiscal Year: 2006
    ..framework for interaction between the dihydropyridine receptor/voltage sensor and the ryanodine receptor (RyR)/Ca release channel, and is essential for the operation of excitation-contraction (E-C) coupling...