ryanodine receptor calcium release channel

Summary

Summary: Protein complexes that mediate the release of calcium from the sarcoplasmic reticulum in both skeletal and cardiac muscle cells by forming tetrametric complexes. These complexes each then act as a calcium channel. There are three isoforms of the RyR: RyR1, RyR2, and RyR3. RyR1 is specifically expressed in skeletal muscles and RyR2 in cardiac muscles. RyR3 is yet another isoform found in non-muscle cells such as neuronal cells. (From Yonsei Med J 1996;37(1):72-80)

Top Publications

  1. ncbi Cardiac excitation-contraction coupling
    Donald M Bers
    Department of Physiology, Stritch School of Medicine, Loyola Unversity Chicago, IL 60153, USA
    Nature 415:198-205. 2002
  2. ncbi Inositol trisphosphate and calcium signalling
    M J Berridge
    AFRC Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, UK
    Nature 361:315-25. 1993
  3. 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
  4. ncbi Effects of diabetes on ryanodine receptor Ca release channel (RyR2) and Ca2+ homeostasis in rat heart
    Nazmi Yaras
    Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
    Diabetes 54:3082-8. 2005
  5. ncbi Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1
    Takashi Kimura
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601, Australia
    Hum Mol Genet 14:2189-200. 2005
  6. pmc Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA
    Nat Med 15:325-30. 2009
  7. ncbi Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees
    M Davis
    Department of Neuropathology, Royal Perth Hospital, Western Australia
    Br J Anaesth 88:508-15. 2002
  8. ncbi Termination of calcium-induced calcium release by induction decay: an emergent property of stochastic channel gating and molecular scale architecture
    D R Laver
    Department of Physiology and Pharmacology, University of Bristol, Bristol BS9 1TH, UK
    J Mol Cell Cardiol 54:98-100. 2013
  9. 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
  10. pmc Dynamic, inter-subunit interactions between the N-terminal and central mutation regions of cardiac ryanodine receptor
    Zheng Liu
    Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA
    J Cell Sci 123:1775-84. 2010

Detail Information

Publications397 found, 100 shown here

  1. ncbi Cardiac excitation-contraction coupling
    Donald M Bers
    Department of Physiology, Stritch School of Medicine, Loyola Unversity Chicago, IL 60153, USA
    Nature 415:198-205. 2002
    ..Furthermore, spatial microdomains within the cell are important in localizing the molecular players that orchestrate cardiac function...
  2. ncbi Inositol trisphosphate and calcium signalling
    M J Berridge
    AFRC Laboratory of Molecular Signalling, Department of Zoology, University of Cambridge, UK
    Nature 361:315-25. 1993
    ..Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling...
  3. 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
    ..6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein, mAKAP. In failing human hearts, RyR2 is PKA hyperphosphorylated, resulting in defective channel function due to increased sensitivity to Ca2+-induced activation...
  4. ncbi Effects of diabetes on ryanodine receptor Ca release channel (RyR2) and Ca2+ homeostasis in rat heart
    Nazmi Yaras
    Department of Biophysics, School of Medicine, Ankara University, Ankara, Turkey
    Diabetes 54:3082-8. 2005
    ..These defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channel (RyR2)...
  5. ncbi Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1
    Takashi Kimura
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601, Australia
    Hum Mol Genet 14:2189-200. 2005
    ..We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle...
  6. pmc Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032, USA
    Nat Med 15:325-30. 2009
    ....
  7. ncbi Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees
    M Davis
    Department of Neuropathology, Royal Perth Hospital, Western Australia
    Br J Anaesth 88:508-15. 2002
    ..Haplotype analysis using chromosome 19q markers indicated that the three families are likely to be unrelated, providing confirmation that the MH/central core disease region 1 of RYR1 is a mutation hot spot...
  8. ncbi Termination of calcium-induced calcium release by induction decay: an emergent property of stochastic channel gating and molecular scale architecture
    D R Laver
    Department of Physiology and Pharmacology, University of Bristol, Bristol BS9 1TH, UK
    J Mol Cell Cardiol 54:98-100. 2013
    ....
  9. 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
    ..CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals.org...
  10. pmc Dynamic, inter-subunit interactions between the N-terminal and central mutation regions of cardiac ryanodine receptor
    Zheng Liu
    Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA
    J Cell Sci 123:1775-84. 2010
    ....
  11. pmc Characterization and temporal development of cores in a mouse model of malignant hyperthermia
    Simona Boncompagni
    Centro Scienze dell Invecchiamento, Department of Basic and Applied Medical Sciences, Interuniversity Institute of Myology, Università Gabriele d Annunzio, I 66013 Chieti, Italy
    Proc Natl Acad Sci U S A 106:21996-2001. 2009
    ....
  12. ncbi The versatility and universality of calcium signalling
    M J Berridge
    The Babraham Institute, Laboratory of Molecular Signalling, Babraham Hall, Babraham, Cambridge, CB2 4AT, UK
    Nat Rev Mol Cell Biol 1:11-21. 2000
    ..Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis...
  13. pmc Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia
    Christian B Jung
    Klinikum rechts der Isar, Technische Universitat Munchen, I Medizinische Klinik, Kardiologie, Munchen, Germany
    EMBO Mol Med 4:180-91. 2012
    ..Our work provides a new in vitro model to study the pathogenesis of human cardiac arrhythmias and develop novel therapies for CPVT...
  14. pmc Ryanodine receptors: structure, expression, molecular details, and function in calcium release
    Johanna T Lanner
    Baylor College of Medicine, Department of Molecular Physiology and Biophysics, Houston, Texas 77030, USA
    Cold Spring Harb Perspect Biol 2:a003996. 2010
    ..This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders...
  15. ncbi The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule
    Ching Chieh Tung
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    Nature 468:585-8. 2010
    ....
  16. pmc Minding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity
    Isaac N Pessah
    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
    Pharmacol Ther 125:260-85. 2010
    ....
  17. 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
    ..Our results indicate that inhibition of the RyR2 open state provides a new therapeutic strategy to prevent diastolic Ca(2+) waves resulting in triggered arrhythmias, such as CPVT...
  18. pmc Redox modification of ryanodine receptors contributes to sarcoplasmic reticulum Ca2+ leak in chronic heart failure
    Dmitry Terentyev
    Departments of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, OH, USA
    Circ Res 103:1466-72. 2008
    ..These findings suggest that redox modification contributes to abnormal function of RyR2s in HF, presenting a potential therapeutic target for treating HF...
  19. ncbi Calcium signaling between sarcolemmal calcium channels and ryanodine receptors in heart cells
    Heping Cheng
    Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Front Biosci 7:d1867-78. 2002
    ..The local stability of CICR is insured because of strong, use-dependent inactivation of RyRs, that terminates Ca2+ sparks and confers persistent local SR refractoriness...
  20. pmc Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release
    Qiang Zhou
    Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
    Nat Med 17:1003-9. 2011
    ..Combining SOICR inhibition with optimal beta blockade has the potential to provide antiarrhythmic therapy that can be tailored to individual patients...
  21. ncbi The sarcoplasmic reticulum and arrhythmogenic calcium release
    Luigi A Venetucci
    Unit of Cardiac Physiology, University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, UK
    Cardiovasc Res 77:285-92. 2008
    ..The review concludes with a description of potential mechanisms for treating arrhythmias produced by Ca(2+) waves...
  22. ncbi A novel FK506 binding protein can mediate the immunosuppressive effects of FK506 and is associated with the cardiac ryanodine receptor
    E Lam
    Department of Immunology Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 270:26511-22. 1995
    ..Our results suggest that FKBP12.6 has both a unique physiological role in excitation-contraction coupling in cardiac muscle and the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin...
  23. pmc Inherited dysfunction of sarcoplasmic reticulum Ca2+ handling and arrhythmogenesis
    Silvia G Priori
    Molecular Cardiology Laboratories, IRCCS Fondazione Salvatore Maugeri, Via Maugeri 10 10A, Pavia, Italy
    Circ Res 108:871-83. 2011
    ..As of today, the interaction between basic scientists and clinicians to understand CPVT and identify new therapeutic strategies is one of the most compelling examples of the importance of translational research in cardiology...
  24. pmc Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation
    Tatiana Adasme
    Centro de Estudios Moleculares de la Célula, Facultad de Medicina, Universidad de Chile, 838 0453 Santiago, Chile
    Proc Natl Acad Sci U S A 108:3029-34. 2011
    ....
  25. ncbi Insecticidal anthranilic diamides: a new class of potent ryanodine receptor activators
    George P Lahm
    DuPont Crop Protection, Stine Haskell Research Center, 1094 Elkton Road, Newark, DE 19711, USA
    Bioorg Med Chem Lett 15:4898-906. 2005
    ..These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented...
  26. ncbi Unique phosphorylation site on the cardiac ryanodine receptor regulates calcium channel activity
    D R Witcher
    Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis 46202
    J Biol Chem 266:11144-52. 1991
    ..In tissues expressing the cardiac isoform of the ryanodine receptor, such as heart and brain, phosphorylation of the Ca2+ release channel by CaM kinase may provide a unique mechanism for regulating intracellular Ca2+ release...
  27. ncbi Ca2+/calmodulin-dependent protein kinase modulates cardiac ryanodine receptor phosphorylation and sarcoplasmic reticulum Ca2+ leak in heart failure
    Xun Ai
    Department of Medicine, University of Illinois at Chicago, IL 60612, USA
    Circ Res 97:1314-22. 2005
    ..Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF...
  28. pmc Three-dimensional electron microscopy reveals new details of membrane systems for Ca2+ signaling in the heart
    Takeharu Hayashi
    The Center for Research in Biological Systems, University of California San Diego, La Jolla, CA 92093, USA
    J Cell Sci 122:1005-13. 2009
    ..g. Ca(2+) sparks)...
  29. ncbi Redox sensitivity of the ryanodine receptor interaction with FK506-binding protein
    Spyros Zissimopoulos
    Wales Heart Research Institute, Department of Cardiology, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom
    J Biol Chem 282:6976-83. 2007
    ..6 dissociation from the RyR2 channel complex, did not restore normal FKBP binding under oxidizing conditions. Our results indicate that the redox state of the RyR is intimately connected with FKBP binding affinity...
  30. pmc New roles of calsequestrin and triadin in cardiac muscle
    Björn C Knollmann
    Depts of Medicine and Pharmacology, Vanderbilt Univ, Nashville, TN 37232, USA
    J Physiol 587:3081-7. 2009
    ....
  31. pmc Anesthetic- and heat-induced sudden death in calsequestrin-1-knockout mice
    Marco Dainese
    Ce S I Department of Basic and Applied Medical Sciences, Interuniversity Institute of Myology, University G D Annunzio, I 66013 Chieti, Italy
    FASEB J 23:1710-20. 2009
    ..These results demonstrate that CASQ1 deficiency alters proper control of RYR1 function and suggest CASQ1 as a potential candidate gene for linkage analysis in families with MH/EHS where mutations in the RYR1 gene are excluded...
  32. pmc Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity
    Andrew M Bellinger
    Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 105:2198-202. 2008
    ..Taken together, these data suggest a possible mechanism by which Ca2+ leak via calstabin1-depleted RyR1 channels leads to defective Ca2+ signaling, muscle damage, and impaired exercise capacity...
  33. ncbi Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum
    W Guo
    Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA
    J Biol Chem 270:9027-30. 1995
    ....
  34. pmc Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients
    A V Postma
    J Med Genet 42:863-70. 2005
    ..The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands...
  35. ncbi Mutations in RYR1 in malignant hyperthermia and central core disease
    Rachel Robinson
    Malignant Hyperthermia Investigation Unit, St James University Hospital, Leeds, United Kingdom
    Hum Mutat 27:977-89. 2006
    ..This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions...
  36. pmc The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues
    G Giannini
    European Molecular Biology Laboratory, Heidelberg, Germany
    J Cell Biol 128:893-904. 1995
    ..This widespread pattern of expression suggests that RyRs may participate in the regulation of intracellular calcium homeostasis in a range of cells wider than previously recognized...
  37. ncbi Calcium-induced calcium release in skeletal muscle
    Makoto Endo
    Saitama Medical University, Saitama, Japan
    Physiol Rev 89:1153-76. 2009
    ....
  38. pmc CaMKII inhibition targeted to the sarcoplasmic reticulum inhibits frequency-dependent acceleration of relaxation and Ca2+ current facilitation
    Eckard Picht
    Department of Physiology, Loyola University Chicago, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA
    J Mol Cell Cardiol 42:196-205. 2007
    ..Thus SR-targeted CaMKII inhibition can directly inhibit the activation of SR Ca(2+) uptake, SR Ca(2+) release and I(Ca) by CaMKII, effects which have all been implicated in triggered arrhythmias...
  39. ncbi CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation
    Stefan Neef
    Department of Cardiology and Pneumology Heart Center, Georg August University Gottingen, Robert Koch Strasse 40, Gottingen, Germany
    Circ Res 106:1134-44. 2010
    ..In ventricular myocardium, ryanodine receptor type 2 (RyR2) phosphorylation by Ca(2+)/calmodulin-dependent protein kinase (CaMK)II is emerging as an important mechanism for SR Ca(2+) leak...
  40. pmc Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice
    Stephan E Lehnart
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 118:2230-45. 2008
    ..Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death...
  41. ncbi Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase
    Jerald Curran
    Rush University Medical Center, Chicago, IL 60611, USA
    Circ Res 100:391-8. 2007
    ..The results suggest that beta-AR stimulation enhances diastolic SR Ca leak in a manner that is (1) CaMKII dependent, (2) not protein kinase A dependent, and 3) not dependent on bulk [Ca](i)...
  42. pmc IP(3) receptors: toward understanding their activation
    Colin W Taylor
    Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, United Kingdom
    Cold Spring Harb Perspect Biol 2:a004010. 2010
    ....
  43. pmc Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice
    Mihail G Chelu
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA
    J Clin Invest 119:1940-51. 2009
    ..Together, these findings suggest that increased RyR2-dependent Ca2+ leakage due to enhanced CaMKII activity is an important downstream effect of CaMKII in individuals susceptible to AF induction...
  44. ncbi Crystal structure of the ligand binding suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor
    Ivan Bosanac
    Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada
    Mol Cell 17:193-203. 2005
    ..The present study sheds light onto the mechanism underlying the receptor's sensitivity to the ligand and its communication with cellular signaling proteins...
  45. ncbi Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane
    L Zhang
    Department of Medicine and the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 272:23389-97. 1997
    ..Taken together, these results suggest that junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release...
  46. ncbi Congenital muscle disorders with cores: the ryanodine receptor calcium channel paradigm
    Susan Treves
    Dipartimento di Medicina Sperimentale e Diagnostica, Universita di Ferrara, 44100 Ferrara, Italy
    Curr Opin Pharmacol 8:319-26. 2008
    ..In this review, we discuss the classes of RYR1 mutations which have been associated with CCD, MmD and related neuromuscular phenotypes...
  47. pmc Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes
    David Baddeley
    Department of Physiology, University of Auckland, Auckland 1142, New Zealand
    Proc Natl Acad Sci U S A 106:22275-80. 2009
    ..We suggest that calcium sparks may be the result of the concerted activation of several RyR clusters forming a functional "supercluster" whose gating is controlled by both cytosolic and sarcoplasmic reticulum luminal calcium levels...
  48. ncbi Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia
    J Fujii
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Science 253:448-51. 1991
    ..Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs...
  49. ncbi Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion
    Nigel F Clarke
    Institute for Neuroscience and Muscle Research, Children s Hospital at Westmead, Sydney, Australia
    Hum Mutat 31:E1544-50. 2010
    ..Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1 are a relatively common cause of CFTD and can be associated with extreme fiber size disproportion...
  50. pmc A mathematical analysis of the generation and termination of calcium sparks
    R Hinch
    University Laboratory of Physiology and Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, Oxford, United Kingdom
    Biophys J 86:1293-307. 2004
    ..Additionally, a model of the coupling of the release channels via the FK-binding protein is analyzed...
  51. ncbi Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor
    N Monnier
    Laboratoire de Biochimie de l ADN, CHU Grenoble, Grenoble, France
    Hum Mol Genet 10:2581-92. 2001
    ..According to a four-transmembrane domain model, the mutations concentrated mostly in the myoplasmic and luminal loops linking, respectively, transmembrane domains T1 and T2 or T3 and T4 of RYR1...
  52. ncbi miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2
    Dmitry Terentyev
    Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, Ohio State University, Columbus, OH 43210, USA
    Circ Res 104:514-21. 2009
    ..We conclude that miR-1 enhances cardiac excitation-contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels...
  53. pmc Differential regulation of SK and BK channels by Ca(2+) signals from Ca(2+) channels and ryanodine receptors in guinea-pig urinary bladder myocytes
    Gerald M Herrera
    Department of Molecular Physiology, University of Vermont College of Medicine, Burlington, VT 05405, USA
    J Physiol 541:483-92. 2002
    ..These results indicate that Ca(2+) entry through VDCCs activates both BK and SK channels, but Ca(2+) release (Ca(2+) sparks) through RyRs activates only BK channels...
  54. ncbi Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure
    Steven Reiken
    Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circulation 107:2459-66. 2003
    ..6. We tested the hypothesis that improved cardiac muscle function attributable to beta-AR blockade is associated with restoration of normal RyR2 channel function in patients with heart failure...
  55. pmc Pernicious attrition and inter-RyR2 CICR current control in cardiac muscle
    Dirk Gillespie
    Rush University Medical Center, Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, 1750 West Harrison Street, Chicago, IL 60612, USA
    J Mol Cell Cardiol 58:53-8. 2013
    ..Moreover, we aggregate RyR data into a working scheme of inter-RyR CICR current control of sparks and a potential inter-RyR CICR termination mechanism that we call pernicious attrition...
  56. ncbi Defective cardiac ryanodine receptor regulation during atrial fibrillation
    John A Vest
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Circulation 111:2025-32. 2005
    ..6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhythmias. Little is known about the role of RyR2 dysfunction in AF, however...
  57. ncbi 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
    ..6 from RyR2, leading to diastolic sarcoplasmic reticulum Ca(2+) leakage and ventricular tachycardia (VT). We tested the hypothesis that FKBP12.6 overexpression in cardiac myocytes can reduce susceptibility to VT in stress conditions...
  58. ncbi Molecular characterization of flubendiamide sensitivity in the lepidopterous ryanodine receptor Ca(2+) release channel
    Kenta Kato
    Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615 8510, Japan
    Biochemistry 48:10342-52. 2009
    ..Our results suggest that the transmembrane domain plays an important role in the formation of an action site for flubendiamide, while the N-terminus is a structural requirement for flubendiamide-induced activation of the sRyR...
  59. 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)...
  60. ncbi Muscle-specific functions of ryanodine receptor channels in Caenorhabditis elegans
    E B Maryon
    Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA
    J Cell Sci 111:2885-95. 1998
    ..elegans sarcoplasmic reticulum. Morphological and behavioral phenotypes of unc-68 mutants suggest that intracellular calcium release is not essential for excitation-contraction coupling in C. elegans...
  61. ncbi Elementary and global aspects of calcium signalling
    M J Berridge
    Babraham Institute Laboratory of Molecular Signalling, Cambridge, UK
    J Exp Biol 200:315-9. 1997
    ....
  62. ncbi Ryanodine receptor physiology and its role in disease
    Johanna T Lanner
    Department of Physiology and Pharmacology, Karolinska Institutet, Von Eulersväg 8, 171 77 Stockholm, Sweden
    Adv Exp Med Biol 740:217-34. 2012
    ..This article discusses the physiological function of RyR and examines its role in disorders and diseases...
  63. 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...
  64. ncbi Viral gene transfer rescues arrhythmogenic phenotype and ultrastructural abnormalities in adult calsequestrin-null mice with inherited arrhythmias
    Marco Denegri
    Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy
    Circ Res 110:663-8. 2012
    ....
  65. pmc Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function
    Sho Kakizawa
    Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    EMBO J 31:417-28. 2012
    ..These findings suggest that NICR via RyR1 plays a regulatory role in the physiological and pathophysiological functions of the brain...
  66. ncbi The deletion of exon 3 in the cardiac ryanodine receptor is rescued by β strand switching
    Paolo A Lobo
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, room 2 320, Vancouver, BC V6T1Z3, Canada
    Structure 19:790-8. 2011
    ..Despite the rescue, the deletion affects interfaces with other RYR2 domains. We propose that relative movement of the NTD is allosterically coupled to the pore region...
  67. ncbi Short communication: flecainide exerts an antiarrhythmic effect in a mouse model of catecholaminergic polymorphic ventricular tachycardia by increasing the threshold for triggered activity
    Nian Liu
    Cardiovascular Genetics Program, Leon H Charney Division of Cardiology, New York University School of Medicine, 522 First Ave, New York, NY 10016, USA
    Circ Res 109:291-5. 2011
    ..It is possible for flecainide to directly affect the cardiac ryanodine receptor (RyR2); however, an extracellular site of action is suggested because of the hydrophilic nature of flecainide...
  68. pmc Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion
    Jeremy Fauconnier
    Institut de la Sante et de la Recherche Medicale, U1046, F 34295 Montpellier, France
    Proc Natl Acad Sci U S A 108:13258-63. 2011
    ..TNF-α-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca(2+) leak trough normalization of RyR2 function is cardioprotective...
  69. ncbi Central core disease due to recessive mutations in RYR1 gene: is it more common than described?
    Patrícia M Kossugue
    Department of Genetics, Human Genome Research Center, IB USP, R do Matão, 106, Sao Paulo, SP CEP 05508 900, Brazil
    Muscle Nerve 35:670-4. 2007
    ..Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families...
  70. pmc Identical de novo mutation in the type 1 ryanodine receptor gene associated with fatal, stress-induced malignant hyperthermia in two unrelated families
    Linda Groom
    Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, USA
    Anesthesiology 115:938-45. 2011
    ..However, cases of sudden death during exertion, heat challenge, and febrile illness in the absence of triggering drugs have been reported. The underlying causes of such drug-free fatal "awake" episodes are unknown...
  71. ncbi Calmodulin binding and inhibition of cardiac muscle calcium release channel (ryanodine receptor)
    D M Balshaw
    Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA
    J Biol Chem 276:20144-53. 2001
    ..Parallel experiments with the skeletal muscle isoform showed major differences in the CaM binding properties and regulation by CaM of the skeletal and cardiac ryanodine receptors...
  72. pmc Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction
    Xiaoping Liu
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Cell 150:1055-67. 2012
    ..Thus, neuronal RyR2 remodeling contributes to stress-induced cognitive dysfunction. Leaky RyR2 could be a therapeutic target for treatment of stress-induced cognitive dysfunction...
  73. ncbi Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies
    Andrea Klein
    Paediatric Neurology, University Children s Hospital Zurich, Zurich, Switzerland
    Hum Mutat 33:981-8. 2012
    ..Assigning pathogenicity to novel mutations is often difficult, and interpretation of genetic results in the context of clinical, histological, and muscle magnetic resonance imaging findings is essential...
  74. pmc Temperature and RyR1 regulate the activation rate of store-operated Ca²+ entry current in myotubes
    Viktor Yarotskyy
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York, USA
    Biophys J 103:202-11. 2012
    ....
  75. pmc Ryanodine receptor current amplitude controls Ca2+ sparks in cardiac muscle
    Tao Guo
    Department of Molecular Biophysics and Physiology, Section of Cellular Signaling, Rush University Medical Center, Chicago, IL 60112, USA
    Circ Res 111:28-36. 2012
    ..The inherent positive feedback of CICR is normally well-controlled. Understanding this control mechanism is a priority because its malfunction has life-threatening consequences...
  76. ncbi Ryanodine receptor interaction with the SNARE-associated protein snapin
    Spyros Zissimopoulos
    Wales Heart Research Institute, Department of Cardiology, Cardiff University School of Medicine, Heath Park, UK
    J Cell Sci 119:2386-97. 2006
    ..Thus, regulation of the association between ryanodine receptor and snapin might constitute part of the elusive molecular mechanism by which ryanodine-sensitive Ca(2+) stores modulate neurosecretion...
  77. ncbi Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells
    R Kohler
    Department of Endocrinology and Nephrology, Medical Center Benjamin Franklin, Freie Universitat Berlin, Berlin, Germany
    Cardiovasc Res 51:160-8. 2001
    ..We hypothesized that expression of ryanodine-receptors (RyR) and TRP channels differs between human endothelium in situ and in cultured cells...
  78. pmc Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathy
    James J Dowling
    Department of Paediatrics, University of Michigan Medical School, Ann Arbor, MI 48109 2200, USA
    Brain 135:1115-27. 2012
    ..We propose that N-acetylcysteine represents the first potential therapeutic strategy for these debilitating muscle diseases...
  79. pmc Ryanodine receptor channelopathies
    Matthew J Betzenhauser
    Department of Physiology, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Pflugers Arch 460:467-80. 2010
    ..Thus, RyR channelopathies are both of interest because they cause significant human diseases and provide model systems that can be studied to elucidate important structure-function relationships of these ion channels...
  80. pmc Subnanometer-resolution electron cryomicroscopy-based domain models for the cytoplasmic region of skeletal muscle RyR channel
    Irina I Serysheva
    National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 105:9610-5. 2008
    ..Taken together, these results provide a structural context for both channel gating and the consequences of certain malignant hyperthermia and central core disease-associated mutations in RyR1...
  81. ncbi Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse
    Mihail G Chelu
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
    FASEB J 20:329-30. 2006
    ..We conclude that the heterozygous expression of the Y522S mutation confers susceptibility to both heat- and anesthetic-induced MH responses...
  82. 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. These results suggest a physical and functional interaction between Ca(v)1.3 and RyR2 and important implications of Ca(v)1.3/RyR2 clusters in translating synaptic activity into alterations in gene expression...
  83. ncbi Homer proteins and InsP(3) receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres
    M Salanova
    Department of Neuroscience, University of Siena, Siena, Italy
    Cell Calcium 32:193-200. 2002
    ..Thus, in skeletal muscle, Homer proteins may play a role in the organisation of a second Ca(2+) signalling compartment containing the InsP(3)R, but are apparently not involved in the organisation of RyRs at triads...
  84. pmc Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure
    Ralph J van Oort
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM335, Houston, TX 77030, USA
    Circulation 122:2669-79. 2010
    ..We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias...
  85. pmc Localization of the dantrolene-binding sequence near the FK506-binding protein-binding site in the three-dimensional structure of the ryanodine receptor
    Ruiwu Wang
    Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 286:12202-12. 2011
    ..6-binding site but distant to the central region around residue Ser-2367. An allosteric mechanism by which dantrolene stabilizes interdomain interactions between the NH2-terminal and central regions is proposed...
  86. ncbi Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12
    W Shou
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nature 391:489-92. 1998
    ..Physiological studies demonstrate that FKBP12 is dispensable for TGF-beta-mediated signalling, but modulates the calcium release activity of both skeletal and cardiac ryanodine receptors...
  87. 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 (CPVT1) in the young...
  88. ncbi Identification of malignant hyperthermia-susceptible ryanodine receptor type 1 gene (RYR1) mutations in a child who died in a car after exposure to a high environmental temperature
    Hajime Nishio
    Department of Legal Medicine, Osaka Medical College, 2 7 Daigaku, Takatsuki 569 8686, Japan
    Leg Med (Tokyo) 11:142-3. 2009
    ..These findings suggest that a MH-susceptible case may have died with a presumed diagnosis of heat stroke at autopsy...
  89. ncbi Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia
    Norma Beatriz Romero
    Inserm U 582 and Institute of Myology, CHU Pitie Salpetriere, Paris, France
    Brain 126:2341-9. 2003
    ..This is the first report of mutations in the RYR1 gene involved in a severe form of CCD presenting as a fetal akinesia syndrome with AD and AR inheritances...
  90. 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
    ..However, the underlying mechanism by which a single mutation in such a large molecule produces drastic effects on channel function remains unresolved...
  91. pmc Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating
    Alexandra Zahradnikova
    Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, 833 34 Bratislava, Slovak Republic
    J Gen Physiol 136:101-16. 2010
    ..This mechanism clarifies the unexpectedly low calcium release flux during elementary release events and unifies the theory of calcium signaling in resting and contracting cardiac myocytes...
  92. ncbi 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
    ..We surmise that a comprehensive characterisation of mutations on a case-by-case basis may be beneficial for the development of specifically targeted therapies...
  93. 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
    ..Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias...
  94. ncbi Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1
    Paula Aracena-Parks
    Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 281:40354-68. 2006
    ..In summary, we have identified a discrete subset of cysteines that are likely to be involved in the functional response of RyR1 to different redox modifications (S-nitrosylation, S-glutathionylation, and oxidation to disulfides)...
  95. pmc Facilitated maturation of Ca2+ handling properties of human embryonic stem cell-derived cardiomyocytes by calsequestrin expression
    Jing Liu
    Stem Cell Program and Department of Cell Biology and Human Anatomy, University of California Davis, Davis, California, USA
    Am J Physiol Cell Physiol 297:C152-9. 2009
    ..We conclude that CSQ expression in hESC-CMs facilitates Ca(2+) handling maturation. Our results shed insights into the suitability of hESC-CMs for therapies and as certain heart disease models for drug screening...
  96. ncbi Single-channel characterization of the rabbit recombinant RyR2 reveals a novel inactivation property of physiological concentrations of ATP
    Richard Stewart
    Department of Physiology and Pharmacology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK
    J Membr Biol 222:65-77. 2008
    ....
  97. pmc Two intracellular pathways mediate metabotropic glutamate receptor-induced Ca2+ mobilization in dopamine neurons
    Hitoshi Morikawa
    Vollum Institute, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Neurosci 23:149-57. 2003
    ..These results demonstrate that an excitatory neurotransmitter glutamate uses multiple intracellular pathways to exert an inhibitory control on the excitability of dopamine neurons...
  98. pmc Absence of transverse tubules contributes to non-uniform Ca(2+) wavefronts in mouse and human embryonic stem cell-derived cardiomyocytes
    Deborah K Lieu
    Human Embryonic Cell Consortium, Stem Cell Program, University of California, Davis, Sacramento, CA 95817, USA
    Stem Cells Dev 18:1493-500. 2009
    ..Immature m and hESC-CMs display unsynchronized Ca(2+) transients due to the absence of t-tubules and gene products crucial for their biogenesis. Our results provide insights for driving the maturation of ESC-CMs...
  99. ncbi Doxorubicin cardiac dysfunction: effects on calcium regulatory proteins, sarcoplasmic reticulum, and triiodothyronine
    Richard D Olson
    Pharmacology and Gerontology Research Unit, Veteran s Affairs Medical Center, 500 W Fort St, Boise, ID 83702, USA
    Cardiovasc Toxicol 5:269-83. 2005
    ..Our results suggest that chronic doxorubicin administration in the rabbit causes a SR-dependent contractile dysfunction that may result, in part, from decreased T3...
  100. ncbi Ryanodine receptors in muscarinic receptor-mediated bronchoconstriction
    Wanglei Du
    Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Medical Center, Durham, North Carolina, 27710, USA
    J Biol Chem 280:26287-94. 2005
    ..Our findings provide new insights into the complex calcium signaling in ASMCs and suggest that RyRs are potential therapeutic targets in bronchospastic disorders such as asthma...
  101. ncbi X-ROS signaling: rapid mechano-chemo transduction in heart
    Benjamin L Prosser
    Center for Biomedical Engineering and Technology BioMET, University of Maryland School of Medicine, Baltimore, MD 21209, USA
    Science 333:1440-5. 2011
    ..X-ROS signaling thus provides a mechanistic explanation for the mechanotransduction of Ca(2+) release in the heart and offers fresh therapeutic possibilities...

Research Grants75

  1. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2013
    ..abstract_text> ..
  2. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2012
    ..abstract_text> ..
  3. Purkinje Origin of Ischemic Ventricular Tachycardia and Fibrillation
    James B Martins; Fiscal Year: 2013
    ..Similarly such drugs may be combined with other antioxidants to prevent dangerous heart rhythms. ..
  4. Neurotrophins in the Lung
    Y S Prakash; Fiscal Year: 2012
    ..By establishing the role of neurotrophins in airway narrowing with or without inflammation, the proposed studies will the foundation for better understanding of airway diseases, and potential development of new therapeutic targets. ..
  5. Local Calcium Signaling in Pulmonary Arteries
    JAMES SK SHAM; Fiscal Year: 2012
    ..The information generated by the proposed experiments will be valuable for the development of new treatments for pulmonary vascular diseases. ..
  6. Function and regulation of elemental Ca2+ signaling in urethral smooth muscle
    Ronghua Zhuge; Fiscal Year: 2013
    ....
  7. Nuclear ryanodine receptor type 1: Role in skeletal muscle physiology and disease
    Viktor Yarotskyy; Fiscal Year: 2013
    ..This project will test the validity of a novel pathophysiological mechanism by which altered RyR1 channel in impacts skeletal muscle disease. ..
  8. Calcium Handling in Cardiac Pathophysiology
    Evangelia G Kranias; Fiscal Year: 2013
    ....
  9. Role of CaMKII Phosphorylation of RyR in Pathological &Physiological Hypertrophy
    Jonathan L Respress; Fiscal Year: 2011
    ..Abnormal Ca2+ regulation in the heart muscle cell could lead to development of HP. In this project, we will use a genetic approach to test whether inhibition of Ca2+ leak leads to prevention of hypertrophy and heart failure development. ..
  10. FKBP Interaction with RYR Calcium Channels in Heart
    Donald M Bers; Fiscal Year: 2013
    ..We will conduct fundamental quantitative molecular fluorescence studies that will clarify both structurally and functionally how FKBP binds to and regulates RyR function in the heart. ..
  11. Genetic Susceptibility to PCB-induced Motor Dysfunction
    CHRISTINE PERDAN CURRAN; Fiscal Year: 2012
    ..The proposed research is designed to identify neural pathways affected by PCB exposure and humans at highest risk of PCB developmental neurotoxicity using a mouse model that mirrors known genetic variations in humans. ..
  12. Ryanodine receptor in cardiac hypertrophy and heart failure
    GERHARD W MEISSNER; Fiscal Year: 2013
    ..Our studies will provide new approaches to minimize the risks of cardiac hypertrophy and heart failure, one of the most frequent causes of death in humans. ..
  13. PCBs, PBDEs, Hearing Loss & Attention/Impulsivity: Mechanistic Studies in Animals
    Susan L Schantz; Fiscal Year: 2010
    ..As in the past, findings from these animal studies will guide the selection of outcome measures for use in the birth cohort. ..
  14. Cardiac Sarcoplasmic Reticulum Calcium Cycling Proteins
    Evangelia G Kranias; Fiscal Year: 2013
    ..Our studies will clearly advance our knowledge on these two protein players involved in cardiac function and dysfunction, which may lead to better therapeutic avenues in heart failure. ..
  15. Roles of voltage sensor, S100A1 and calmodulin in skeletal muscle Ca2+ signaling
    Martin F Schneider; Fiscal Year: 2013
    ..Thus, this project has high impact for multiple disciplines, and for problems of both locomotion and breathing common to a variety of advanced diseased states and aging. ..
  16. Dietary Omega-3 Fatty Acids and Sudden Cardiac Death
    GEORGE EDWARD BILLMAN; Fiscal Year: 2010
    ..This project will also determine the effectiveness of fish oil supplements in reducing sudden death due to a lethal abnormal heart rhythm after a heart attack. ..
  17. ALLOSTERIC SITE STRUCTURES OF CARDIOVASCULAR CHANNELS
    Arthur Karlin; Fiscal Year: 2011
    ..The results will provide insights into the molecular mechanisms of allosteric interactions in these two channels and will provide molecular structural bases for cardiovascular therapeutics targeted at these channels. ..
  18. MITOCHONDRIAL CA2+ TRANSPORT IN HEART CELLS
    Shey Shing Sheu; Fiscal Year: 2010
    ..abstract_text> ..
  19. Site-Directed Oxidative Modification of Muscle Protein Structural Dynamics
    David D Thomas; Fiscal Year: 2013
    ..This fundamental information is required for further progress in understanding the structural biology of protein oxidation. ..
  20. CaMK: central regulators of the inflammatory response to surgical sepsis
    MATTHEW RANDALL ROSENGART; Fiscal Year: 2013
    ....
  21. Role of Presenilins in the Synapse
    Jie Shen; Fiscal Year: 2013
    ..Completion of our proposed study will provide insights into AD pathogenesis and may identify novel therapeutic targets for development of new drugs. ..
  22. Genomics and pharmacodynamics of statin-related rhabdomyolysis
    Bruce M Psaty; Fiscal Year: 2013
    ..For validation and translational work, co- investigators will use variants discovered by exome sequencing and replicated by our UK collaborators to conduct basic-science studies and evaluate their function. ..
  23. Calsequestrin in Ventricular Arrhythmia and Sudden Death
    Bjorn C Knollmann; Fiscal Year: 2013
    ..To test the hypothesis that Casq2 is reduced near RyR2 Ca release channels in cardiac muscle surviving after myocardial infarction ..
  24. The Role of Small Ankyrin 1 in the Sarcoplasmic Reticulum in Skeletal Muscle
    Andrew P Ziman; Fiscal Year: 2011
    ..My studies should provide insights into the mechanisms underlying the organization of the calcium stores, changes in which have been implicated in a range of diseases in heart and skeletal muscle. ..
  25. Structural Basis of Dysfunctional Calcium Release Channels in Heart Disease
    Zheng Liu; Fiscal Year: 2013
    ....
  26. CONTROLLED AND UNCONTROLLABLE CALCIUM RELEASE IN HEART
    Sandor Gyorke; Fiscal Year: 2013
    ..S. This proposal will study how improper regulation of calcium by the muscle cells of the heart contributes to arrhythmias. Information gained from this study may help design better therapies for arrhythmias. ..
  27. Rational Design of New Drugs to Treat Ventricular Arrhythmias
    Jonathan J Abramson; Fiscal Year: 2012
    ..In order to meet the urgent need for effective therapeutics, ELEX Biotech will create new more potent medications to treat ventricular arrhythmias via a novel approach toward drug design. ..
  28. Analysis of a Novel Regulator of Excitation-Contraction Coupling in Skeletal Musc
    John Y Kuwada; Fiscal Year: 2013
    ..This knowledge should help us better understand the biology of myopathies and could potentially lead to therapeutic agents for congenital myopathies. ..
  29. Regulation of sarcoplasmic reticulum calcium release in heart failure
    Xander H T Wehrens; Fiscal Year: 2012
    ..The animal models developed for this project may be particularly useful for the development of new drugs for the treatment of congestive heart failure, the leading cause of death in the United States. ..
  30. Molecular Mechanisms of RyR2-triggered Arrhythmias
    Hector H Valdivia; Fiscal Year: 2013
    ..abstract_text> ..
  31. Muscle: Excitation/Contraction Coupling Gordon Research Conference
    Paul D Allen; Fiscal Year: 2011
    ....
  32. Structure of Channels in Excitation-Contracting Coupling
    TERENCE C WAGENKNECHT; Fiscal Year: 2013
    ..This proposal will use advanced electron microscopy technology to characterize the structural organization and interactions among these proteins. The findings will be important for understanding normal and diseased muscle function. ..
  33. Isoform-Specific Regulation of Skeletal Muscle Calcium Channel by Calmodulin
    Naohiro Yamaguchi; Fiscal Year: 2013
    ..In addition, we will screen an additional domain of RyR1 which interacts with CaMLD using protein overlays and surface plasmon resonance. The research will advance understanding of the domain complex involved in CaM regulation of RyR1. ..
  34. Cannabinoid mobilization in neurons (R15DA021683)
    Masako Isokawa; Fiscal Year: 2013
    ....
  35. HORMONAL INTEGRATION OF EXOCRINE AND ENDOCRINE ORGANS
    S MURTHY KARNAM; Fiscal Year: 2013
    ..The innovative aspects of this proposal lie in the discovery of mechanisms of hypercontractility of longitudinal muscle during inflammation. ..
  36. Calcium Entrained Arrhythmias
    RAIMOND LESTER WINSLOW; Fiscal Year: 2013
    ..The proposed work will provide new understanding of the molecular and cellular causes of these heart rhythm disturbances and enable new treatments. ..
  37. Enantioselective Metabolism Influences PCB Developmental Neurotoxicity
    Isaac N Pessah; Fiscal Year: 2013
    ....
  38. Mechanism for Regulation of Phospholipase C by G Protein
    Alan V Smrcka; Fiscal Year: 2013
    ..We will explore these mechanisms further in a whole animal model system with cardiac myocyte specific deletion of PLCe. ..
  39. Structure Function Studies of RyR1 in a Myogenic Knockout
    Paul D Allen; Fiscal Year: 2010
    ..abstract_text> ..
  40. Stretch-Dependent Calcium Signaling in Heart
    WILLIAM JONATHAN LEDERER; Fiscal Year: 2013
    ..Furthermore it will lay the foundation for novel therapies for diverse heart diseases including Duchenne muscular dystrophy. ..
  41. Abnormal Intracellular Calcium Release in Heart Failure
    Sandor Gyorke; Fiscal Year: 2013
    ....
  42. Molecular basis of Ca2+ leak in heart
    GEORGE BLAIR WILLIAMS; Fiscal Year: 2013
    ..For the PI, the investigation nicely supports his long-term plan to combine theoretical investigations with practical and informative tests with the prospect of broadening our understanding of cardiac cellular function. ..
  43. Molecular and Cellular Basis of PCB Developmental Neurotoxicity
    Isaac N Pessah; Fiscal Year: 2013
    ..abstract_text> ..
  44. Ion Transport by Skeletal Muscle Ryanodine Receptor
    GERHARD W MEISSNER; Fiscal Year: 2013
    ..As our studies progress we expect to gain new insights in the complex mechanism of RyR1 opening, ion conductance and selectivity and how these processes are altered by mutations in RyR1 linked to core myopathies. ..
  45. Novel Mechanism of SR Calcium Regulation in Cardiac Dysfunction
    Yibin Wang; Fiscal Year: 2013
    ..Investigation of a novel phosphatase for PLN, a key regulator of SR calcium cycling can bring new insights to the regulatory network in this process and helps to explore new avenues of therapy for heart failure. ..
  46. Structural Studies of RyR Channel
    Irina I Serysheva; Fiscal Year: 2013
    ..The methods developed, as part of this research, will have broad applicability to studies of other ion channels and large membrane protein complexes in near-native state. ..
  47. Remodeling of the Transverse Tubular System and Ryanodine Receptor Clusters in Dy
    FRANK BERND SACHSE; Fiscal Year: 2013
    ..Finally, we will investigate the hypothesis that the probability of spontaneous release events in CRT cells is increased due to up-regulation of adrenergic receptors. ..
  48. Structural/functional interaction between RyR1 and DHPR alpha1s and Beta1a isofor
    Claudio F Perez; Fiscal Year: 2012
    ....
  49. TROPONIN MODULATION IN HEART FAILURE
    Beata M Wolska; Fiscal Year: 2013
    ..The new mechanism is likely to add to our understanding of heart failure, when pressure and ejection of blood is disturbed. Moreover, the new mechanism may lead to development of novel therapies for heart failure. ..
  50. MOLECULAR BASIS OF HEART FAILURE
    ANDREW ROBERT MARKS; Fiscal Year: 2013
    ..The proposed studies are significant because they will provide novel insights concerning the mechanisms of HF progression. ..
  51. Molecular Basis and Treatment of Cardiac Arrhythmias
    SUI RONG WAYNE CHEN; Fiscal Year: 2013
    ..abstract_text> ..
  52. Conformational measurements of RyR1 using a site-specific labeling method
    James D Fessenden; Fiscal Year: 2013
    ..These experiments should provide unprecedented glimpses of the structure of RyR1 and how this structure is perturbed by disease-causing mutations. ..
  53. Low ph alters intracellular and extracellular communication in the acinar cell
    ANAMIKA MARAGRET REED; Fiscal Year: 2013
    ....
  54. Chemobiologic Approach to NAADP Signaling
    James T Slama; Fiscal Year: 2012
    ..It will contribute to understanding fertilization, insulin secretion, smooth muscle contraction, and other important processes. ..
  55. Regulation and Function of Internal Ca2+ Stores in Nerve Terminals
    John V Walsh; Fiscal Year: 2010
    ..There are two general possibilities - that syntillas suppress full fusion events, allowing only partial emptying of a synaptic vesicle. Or the syntillas may suppress release of a population of larger vesicles - or both. ..
  56. Novel Therapeutic Approaches to Atrial Fibrillation Targeting Intracellular Calci
    ANDREW ROBERT MARKS; Fiscal Year: 2013
    ..A rycal is now in Phase II clinical studies for heart failure and sudden cardiac death and would be available for testing in AF patients. ..
  57. Hypertension Pharmacogenetics
    Julie Johnson; Fiscal Year: 2006
    ..The proposed studies should add substantial new information about antihypertensive pharmacogenetics, and could influence how antihypertensive medications are prescribed in the future. ..
  58. Calcium Triggered Arrhythmias and Sudden Cardiac Arrest
    Richard L Moss; Fiscal Year: 2013
    ..Our uniquely complementary approaches will yield new information concerning genetic and sub-cellular processes that confer increased risk for sudden cardiac arrest in heritable cardiac diseases in humans. ..
  59. Ryanodine Receptor in Pancreatitis
    Sohail Z Husain; Fiscal Year: 2013
    ..abstract_text> ..
  60. Control Mechanisms of Ca2+-Induced Ca2+ Release
    Michael Fill; Fiscal Year: 2013
    ..Here, we define local control mechanisms that govern intracellular calcium release as these are potential sites of pathological failure and/or therapeutic intervention. ..
  61. Intracellular calcium leak and muscle function
    ANDREW ROBERT MARKS; Fiscal Year: 2013
    ..The proposed studies are significant because they may identify a novel mechanism underlying intracellular Ca2+ leak that contributes to pathology in MD and could be a therapeutic target in patients. ..
  62. Modeling of Cardiac Calcium Dynamics;Ryanodine Receptor induced Arrhythmias
    Daisuke Sato; Fiscal Year: 2013
    ..3) how susceptibility of triggered activity in tissue can be estimated from the RyR properties. ..
  63. VISUALIZATION OF BIOLOGICAL COMPLEXITY RESOURCE
    Carmen A Mannella; Fiscal Year: 2010
    ..abstract_text> ..
  64. CA2+ RELEASE CHANNEL FROM CARDIAC SARCOPLASMIC RETICULUM
    Kevin Campbell; Fiscal Year: 1991
    ....
  65. REGULATION OF SARCOPLASMIC RETICULUM CA2+ RELEASE
    Gerhard Meissner; Fiscal Year: 2009
    ..abstract_text> ..
  66. CD38/ADP RIBOSYL CYCLASE R0LE IN OSTEOCLAST REGULATION
    Mone Zaidi; Fiscal Year: 2003
    ..Taken together, the studies should provide mechanistic insights into the role of the NAD+/CD38/cADPr/Ca2+ system in osteoclast control. ..
  67. Volatile Anesthesic Inhibition of Ca2+ Release in Airway
    Gary Sieck; Fiscal Year: 2006
    ..The studies will initially focus on the effects of halothane; however, when significant effects are observed, the effects of isoflurane and sevoflurane will also be explored. ..
  68. Molecular Mechanisms of Ventricular Fibrillation
    JOSE JALIFE; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  69. Role of MG29 in E-C Coupling of Striated Muscles
    Jianjie Ma; Fiscal Year: 2006
    ..In addition, our studies with the mutant mice will provide new insights into the cellular mechanism of muscle exercise physiology and cardiovascular diseases. ..
  70. Anthracycline cardiotoxicity and calsequestrin function
    SUSAN SHADLE; Fiscal Year: 2002
    ..the mechanism of inhibition, with particular attention to the roles of calsequestrin and the ryanodine receptor calcium release channel. Comparison of the anthracyclines daunorubicin, daunorubicinol and 5-iminodaunorubicin, which ..
  71. SUBSPECIALIZATION OF CARDIAC SARCOPLASMIC RETICULUM
    Larry Jones; Fiscal Year: 2006
    ..New animal models useful for investigation of cardiac hypertrophy and heart failure will result. ..
  72. REGULATION OF RYANODINE RECEPTOR BY NITROGEN OXIDES
    Jerry Eu; Fiscal Year: 2003
    ..Our results may lead to new insights into regulation of Ca2+ homeostasis in muscle and to the dysregulation of Ca2+ characteristic of disease states such as respiratory failure and rhabdomyolysis. ..
  73. MOLECULAR ANALYSIS OF INSP3 RECEPTOR STRUCTURE FUNCTION
    Gregory Mignery; Fiscal Year: 1999
    ....
  74. A FRET-based assay to measure dynamic changes in RyR1 structure
    JAMES FESSENDEN; Fiscal Year: 2009
    ..This technique will open the door for further structural measurements of RyR1 to determine how disease-causing mutations alter the structure of the channel. ..
  75. Coupled gating between intracellular calcium release ch*
    Andrew Marks; Fiscal Year: 2004
    ..Pharmacologic manipulation, targeted at the regulation of these channels, could ultimately provide novel approaches to treating these and other diseases. ..