Ryr2

Summary

Gene Symbol: Ryr2
Description: ryanodine receptor 2, cardiac
Alias: 9330127I20Rik, RYR-2, ryanodine receptor 2, calcium release channel, cardiac muscle ryanodine receptor, cardiac muscle ryanodine receptor-calcium release channel, ryanodine receptor type 2, type 2 ryanodine receptor
Species: mouse
Products:     Ryr2

Top Publications

  1. Matalon R, Surendran S, McDonald J, Okorodudu A, Tyring S, Michals Matalon K, et al. Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring. Int J Immunopathol Pharmacol. 2005;18:557-65 pubmed
    ..One step real time RT-PCR showed a reduction in cardiac troponin I, troponin T2 and ryanodine receptor 2. Determination of troponin I and T protein levels showed reduced levels of these proteins...
  2. Fauconnier J, Thireau J, Reiken S, Cassan C, Richard S, Matecki S, et al. Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy. Proc Natl Acad Sci U S A. 2010;107:1559-64 pubmed publisher
    ..and functional remodeling of the cardiac sarcoplasmic reticulum (SR) Ca(2+) release channel/ryanodine receptor (RyR2) occurs in the mdx mouse model of DMD. RyR2 from mdx hearts were S-nitrosylated and depleted of calstabin2 (FKBP12...
  3. Zhang Y, Wu J, Jeevaratnam K, King J, Guzadhur L, Ren X, et al. Conduction slowing contributes to spontaneous ventricular arrhythmias in intrinsically active murine RyR2-P2328S hearts. J Cardiovasc Electrophysiol. 2013;24:210-8 pubmed publisher
    ..It is associated with mutations involving the cardiac ryanodine receptor (RyR2)...
  4. Johnson J, Han Z, Otani K, Ye H, Zhang Y, Wu H, et al. RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. J Biol Chem. 2004;279:24794-802 pubmed
    Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis...
  5. Luciani D, Gwiazda K, Yang T, Kalynyak T, Bychkivska Y, Frey M, et al. Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell death. Diabetes. 2009;58:422-32 pubmed publisher
    ..Our results also suggest the involvement of mitochondria in beta-cell apoptosis associated with dysfunctional beta-cell ER Ca(2+) homeostasis and ER stress. ..
  6. Yang H, Tweedie D, Wang S, Guia A, Vinogradova T, Bogdanov K, et al. The ryanodine receptor modulates the spontaneous beating rate of cardiomyocytes during development. Proc Natl Acad Sci U S A. 2002;99:9225-30 pubmed
    ..depressed in ES cell-derived cardiomyocytes with a functional knockout (KO) of the cardiac ryanodine receptor (RyR2). KO myocytes show a slowing of the rate of spontaneous diastolic depolarization and an absence of calcium sparks...
  7. Li N, Wang T, Wang W, Cutler M, Wang Q, Voigt N, et al. Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circ Res. 2012;110:465-70 pubmed publisher
    ..To test the hypothesis that inhibition of CaMKII-phosphorylated type-2 ryanodine receptors (RyR2) prevents AF initiation in FKBP12.6-deficient (-/-) mice. Mice lacking RyR2-stabilizing subunit FKBP12...
  8. Liu X, Betzenhauser M, Reiken S, Meli A, Xie W, Chen B, et al. Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell. 2012;150:1055-67 pubmed publisher
    The type 2 ryanodine receptor/calcium release channel (RyR2), required for excitation-contraction coupling in the heart, is abundant in the brain...
  9. Zhao M, Li P, Li X, Zhang L, Winkfein R, Chen S. Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem. 1999;274:25971-4 pubmed
    ..These data suggest that this conserved region constitutes an essential part of the ryanodine binding site and the channel conduction pathway of the ryanodine receptor. ..

More Information

Publications78

  1. Liu N, Colombi B, Memmi M, Zissimopoulos S, Rizzi N, Negri S, et al. Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model. Circ Res. 2006;99:292-8 pubmed
    ..disease characterized by life threatening arrhythmias and mutations in the gene encoding the ryanodine receptor (RyR2)...
  2. Wehrens X, Lehnart S, Reiken S, Deng S, Vest J, Cervantes D, et al. Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science. 2004;304:292-6 pubmed
    ..6) from the ryanodine receptor-calcium release channel (RyR2) complex causes an intracellular Ca2+ leak that can trigger fatal cardiac arrhythmias...
  3. Kannankeril P, Mitchell B, Goonasekera S, Chelu M, Zhang W, Sood S, et al. Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy. Proc Natl Acad Sci U S A. 2006;103:12179-84 pubmed
    Mutations in the cardiac ryanodine receptor 2 (RyR2) have been associated with catecholaminergic polymorphic ventricular tachycardia and a form of arrhythmogenic right ventricular dysplasia...
  4. Bround M, Asghari P, Wambolt R, Bohunek L, Smits C, Philit M, et al. Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice. Cardiovasc Res. 2012;96:372-80 pubmed publisher
    ..While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction coupling, the role of these ..
  5. Jiang D, Wang R, Xiao B, Kong H, Hunt D, Choi P, et al. 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. Circ Res. 2005;97:1173-81 pubmed
    Ventricular tachycardia (VT) is the leading cause of sudden death, and the cardiac ryanodine receptor (RyR2) is emerging as an important focus in its pathogenesis...
  6. Liu N, Denegri M, Ruan Y, Avelino Cruz J, Perissi A, Negri S, et al. Short communication: flecainide exerts an antiarrhythmic effect in a mouse model of catecholaminergic polymorphic ventricular tachycardia by increasing the threshold for triggered activity. Circ Res. 2011;109:291-5 pubmed publisher
    ..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...
  7. Cerrone M, Noujaim S, Tolkacheva E, Talkachou A, O Connell R, Berenfeld O, et al. Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2007;101:1039-48 pubmed
    ..Catecholaminergic polymorphic VT is caused by enhanced Ca2+ release through defective ryanodine receptor (RyR2) channels...
  8. George C, Higgs G, Lai F. Ryanodine receptor mutations associated with stress-induced ventricular tachycardia mediate increased calcium release in stimulated cardiomyocytes. Circ Res. 2003;93:531-40 pubmed
    Ca2+ release from the sarcoplasmic reticulum mediated by the cardiac ryanodine receptor (RyR2) is a fundamental event in cardiac muscle contraction...
  9. Cerrone M, Colombi B, Santoro M, di Barletta M, Scelsi M, Villani L, et al. Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor. Circ Res. 2005;96:e77-82 pubmed
    ..The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor...
  10. Shan J, Xie W, Betzenhauser M, Reiken S, Chen B, Wronska A, et al. Calcium leak through ryanodine receptors leads to atrial fibrillation in 3 mouse models of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2012;111:708-17 pubmed publisher
    ..The ryanodine receptor (RyR2) is the major calcium (Ca2+) release channel on the sarcoplasmic reticulum (SR) required for excitation-contraction ..
  11. Chelu M, Sarma S, Sood S, Wang S, van Oort R, Skapura D, et al. Calmodulin kinase II-mediated sarcoplasmic reticulum Ca2+ leak promotes atrial fibrillation in mice. J Clin Invest. 2009;119:1940-51 pubmed
    ..Here, we have shown that mice with a genetic gain-of-function defect in Ryr2 (which we termed Ryr2R176Q/+ mice) did not exhibit spontaneous AF but that rapid atrial pacing unmasked an ..
  12. Lobo P, Kimlicka L, Tung C, Van Petegem F. The deletion of exon 3 in the cardiac ryanodine receptor is rescued by ? strand switching. Structure. 2011;19:790-8 pubmed publisher
    Mutations in the cardiac Ryanodine Receptor (RYR2) are linked to triggered arrhythmias. Removal of exon 3 results in a severe form of catecholaminergic polymorphic ventricular tachycardia (CPVT)...
  13. Li P, Chen S. Molecular basis of Ca(2)+ activation of the mouse cardiac Ca(2)+ release channel (ryanodine receptor). J Gen Physiol. 2001;118:33-44 pubmed
    Activation of the cardiac ryanodine receptor (RyR2) by Ca(2)+ is an essential step in excitation-contraction coupling in heart muscle. However, little is known about the molecular basis of activation of RyR2 by Ca(2)+...
  14. Respress J, van Oort R, Li N, Rolim N, Dixit S, Dealmeida A, et al. Role of RyR2 phosphorylation at S2814 during heart failure progression. Circ Res. 2012;110:1474-83 pubmed publisher
    ..However, the importance of CaMKII phosphorylation of ryanodine receptors (RyR2) in HF development and associated diastolic sarcoplasmic reticulum Ca(2+) leak is unclear.
  15. Zhang Y, Fraser J, Jeevaratnam K, Hao X, Hothi S, Grace A, et al. Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts. Cardiovasc Res. 2011;89:794-804 pubmed publisher
    ..explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2(+/S)) and homozygotic (RyR2(S/S)) RyR2-P2328S murine models for catecholaminergic polymorphic ventricular ..
  16. Uchinoumi H, Yano M, Suetomi T, Ono M, Xu X, Tateishi H, et al. Catecholaminergic polymorphic ventricular tachycardia is caused by mutation-linked defective conformational regulation of the ryanodine receptor. Circ Res. 2010;106:1413-24 pubmed publisher
    ..tachycardia (CPVT) is caused by a single point mutation in a well-defined region of the cardiac type 2 ryanodine receptor (RyR)2...
  17. King J, Wickramarachchi C, Kua K, Du Y, Jeevaratnam K, Matthews H, et al. Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation. Cardiovasc Res. 2013;99:751-9 pubmed publisher
    Recent studies reported slowed conduction velocity (CV) in murine hearts homozygous for the gain-of-function RyR2-P2328S mutation (RyR2(S/S)) and associated this with an increased incidence of atrial and ventricular arrhythmias...
  18. Wang Y, Zheng Y, Mei Q, Wang Q, Collier M, Fleischer S, et al. FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am J Physiol Cell Physiol. 2004;286:C538-46 pubmed
    ..Here we show that FK506 binding protein of 12.6 kDa (FKBP12.6) associates with and regulates type 2 RyRs (RyR2) in tracheal smooth muscle. FKBP12...
  19. Liu Z, Wang R, Zhang J, Chen S, Wagenknecht T. Localization of a disease-associated mutation site in the three-dimensional structure of the cardiac muscle ryanodine receptor. J Biol Chem. 2005;280:37941-7 pubmed
    The cardiac muscle ryanodine receptor (RyR2) functions as a calcium release channel in the heart. Up to 40 mutations in RyR2 have been linked to genetic forms of sudden cardiac death...
  20. Takeshima H, Yamazawa T, Ikemoto T, Takekura H, Nishi M, Noda T, et al. Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor. EMBO J. 1995;14:2999-3006 pubmed
    ..Although RyR-3 does not mediate excitation-contraction coupling of the skeletal muscle type, we propose that RyR-3 may induce intracellular Ca2+ release in response to a Ca2+ rise with a high threshold. ..
  21. Goddard C, Ghais N, Zhang Y, Williams A, Colledge W, Grace A, et al. Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts. Acta Physiol (Oxf). 2008;194:123-40 pubmed publisher
    To explore the physiological consequences of the ryanodine receptor (RyR2)-P2328S mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT)...
  22. Takeshima H, Komazaki S, Hirose K, Nishi M, Noda T, Iino M. Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. EMBO J. 1998;17:3309-16 pubmed
    The ryanodine receptor type 2 (RyR-2) functions as a Ca2+-induced Ca2+ release (CICR) channel on intracellular Ca2+ stores and is distributed in most excitable cells with the exception of skeletal muscle cells...
  23. Johnson J, Kuang S, Misler S, Polonsky K. Ryanodine receptors in human pancreatic beta cells: localization and effects on insulin secretion. FASEB J. 2004;18:878-80 pubmed
  24. Giannini G, Conti A, Mammarella S, Scrobogna M, Sorrentino V. The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. J Cell Biol. 1995;128:893-904 pubmed
    ..RyR mRNAs were also detected in in vitro-cultured cell lines. RyR1, RyR2, and RyR3 mRNA were detected in the cerebrum and in the cerebellum...
  25. Xiao B, Zhong G, Obayashi M, Yang D, Chen K, Walsh M, et al. Ser-2030, but not Ser-2808, is the major phosphorylation site in cardiac ryanodine receptors responding to protein kinase A activation upon beta-adrenergic stimulation in normal and failing hearts. Biochem J. 2006;396:7-16 pubmed
    We have recently shown that RyR2 (cardiac ryanodine receptor) is phosphorylated by PKA (protein kinase A/cAMP-dependent protein kinase) at two major sites, Ser-2030 and Ser-2808...
  26. Wehrens X, Lehnart S, Huang F, Vest J, Reiken S, Mohler P, et al. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell. 2003;113:829-40 pubmed
    ..In cardiac muscle, the ryanodine receptor (RyR2) on the sarcoplasmic reticulum releases the calcium required for muscle contraction...
  27. Tang Y, Tian X, Wang R, Fill M, Chen S. Abnormal termination of Ca2+ release is a common defect of RyR2 mutations associated with cardiomyopathies. Circ Res. 2012;110:968-77 pubmed publisher
    Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) have been associated with both cardiac arrhythmias and cardiomyopathies...
  28. Tiso N, Stephan D, Nava A, Bagattin A, Devaney J, Stanchi F, et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Hum Mol Genet. 2001;10:189-94 pubmed
    ..genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families...
  29. Wang R, Zhang L, Bolstad J, Diao N, Brown C, Ruest L, et al. Residue Gln4863 within a predicted transmembrane sequence of the Ca2+ release channel (ryanodine receptor) is critical for ryanodine interaction. J Biol Chem. 2003;278:51557-65 pubmed
    ..Each amino acid residue within the TM10 sequence, 4844IIFDITFFFFVIVILLAIIQGLII4867, of the mouse RyR2 was mutated to either alanine or glycine...
  30. Bai Y, Jones P, Guo J, Zhong X, Clark R, Zhou Q, et al. Phospholamban knockout breaks arrhythmogenic Ca²? waves and suppresses catecholaminergic polymorphic ventricular tachycardia in mice. Circ Res. 2013;113:517-26 pubmed publisher
    ..An important question is whether these seemingly paradoxical effects of PLN-KO exacerbate or protect against Ca²?-triggered arrhythmias...
  31. Lehnart S, Mongillo M, Bellinger A, Lindegger N, Chen B, Hsueh W, et al. Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest. 2008;118:2230-45 pubmed publisher
    The Ca2+ release channel ryanodine receptor 2 (RyR2) is required for excitation-contraction coupling in the heart and is also present in the brain...
  32. Yamaguchi N, Takahashi N, Xu L, Smithies O, Meissner G. Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel. J Clin Invest. 2007;117:1344-53 pubmed
    ..have shown that calmodulin (CaM) inhibits the activity of cardiac muscle cell Ca(2+) release channel ryanodine receptor 2 (RyR2)...
  33. Bround M, Wambolt R, Luciani D, Kulpa J, Rodrigues B, Brownsey R, et al. Cardiomyocyte ATP production, metabolic flexibility, and survival require calcium flux through cardiac ryanodine receptors in vivo. J Biol Chem. 2013;288:18975-86 pubmed publisher
    ..We report that controlled in vivo depletion of cardiac RYR2, using a conditional gene knock-out strategy (cRyr2KO mice), is sufficient to reduce mitochondrial Ca(2+) and ..
  34. van Oort R, McCauley M, Dixit S, Pereira L, Yang Y, Respress J, et al. Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation. 2010;122:2669-79 pubmed publisher
    ..Although abnormal Ca(2+) release from the sarcoplasmic reticulum through ryanodine receptors (RyR2) has been linked to arrhythmogenesis, the molecular mechanisms triggering release of arrhythmogenic Ca(2+) remain ..
  35. Fernandez Velasco M, Rueda A, Rizzi N, Benitah J, Colombi B, Napolitano C, et al. Increased Ca2+ sensitivity of the ryanodine receptor mutant RyR2R4496C underlies catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2009;104:201-9, 12p following 209 pubmed publisher
    Cardiac ryanodine receptor (RyR2) mutations are associated with autosomal dominant catecholaminergic polymorphic ventricular tachycardia, suggesting that alterations in Ca(2+) handling underlie this disease...
  36. Bertocchini F, Ovitt C, Conti A, Barone V, Scholer H, Bottinelli R, et al. Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles. EMBO J. 1997;16:6956-63 pubmed
    ..The disproportion between the low amount of RyR3 and the large impact of the RyR3 knockout suggests that this isoform contributes to the amplification of Ca2+ released by the existing population of ryanodine receptors (RyR1). ..
  37. Zhou Q, Xiao J, Jiang D, Wang R, Vembaiyan K, Wang A, et al. Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release. Nat Med. 2011;17:1003-9 pubmed publisher
    ..tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2)...
  38. Loaiza R, Benkusky N, Powers P, HACKER T, Noujaim S, Ackerman M, et al. Heterogeneity of ryanodine receptor dysfunction in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circ Res. 2013;112:298-308 pubmed publisher
    Most cardiac ryanodine receptor (RyR2) mutations associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) are postulated to cause a distinctive form of Ca(2+) release dysfunction...
  39. Hwang H, Hasdemir C, Laver D, Mehra D, Turhan K, Faggioni M, et al. Inhibition of cardiac Ca2+ release channels (RyR2) determines efficacy of class I antiarrhythmic drugs in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2011;4:128-35 pubmed publisher
    ..polymorphic ventricular tachycardia (CPVT) is caused by mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin (Casq2) and can be difficult to treat...
  40. Mi T, Xiao Z, Guo W, Tang Y, Hiess F, Xiao J, et al. Role of Cys³⁶⁰² in the function and regulation of the cardiac ryanodine receptor. Biochem J. 2015;467:177-90 pubmed publisher
    The cardiac Ca²⁺ release channel [ryanodine receptor type 2 (RyR2)] is modulated by thiol reactive agents, but the molecular basis of RyR2 modulation by thiol reagents is poorly understood...
  41. Chopra N, Yang T, Asghari P, Moore E, Huke S, Akin B, et al. Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A. 2009;106:7636-41 pubmed publisher
    ..2) triggers Ca(2+) release from juxtaposed Ca(2+) release channels (RyR2) located in junctional sarcoplasmic reticulum (jSR)...
  42. Lavorato M, Huang T, Iyer V, Perni S, Meissner G, Franzini Armstrong C. Dyad content is reduced in cardiac myocytes of mice with impaired calmodulin regulation of RyR2. J Muscle Res Cell Motil. 2015;36:205-14 pubmed publisher
    ..2; ryr2, serca2, pmca)...
  43. Kurokawa K, Mizuno K, Ohkuma S. Increase of type 2 ryanodine receptors in mouse nucleus accumbens in the development and expression of morphine-induced place preference. J Pharmacol Sci. 2014;126:285-90 pubmed
    ..The expression of morphine-induced CPP was abolished by dantrolene administration before the post-conditioning test. These findings suggest that RyRs-2 in the NAcc participate in the development and expression of morphine-induced CPP. ..
  44. Fauconnier J, Meli A, Thireau J, Roberge S, Shan J, Sassi Y, et al. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci U S A. 2011;108:13258-63 pubmed publisher
    ..At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca(2+) leak...
  45. Liu Q, Zheng Y, Korde A, Li X, Ma J, Takeshima H, et al. Protein kinase C-epsilon regulates local calcium signaling in airway smooth muscle cells. Am J Respir Cell Mol Biol. 2009;40:663-71 pubmed publisher
    ..Modification of RyR2 activity by FK506-binding protein 12...
  46. Anthony D, Beattie J, Paul A, Currie S. Interaction of calcium/calmodulin-dependent protein kinase IIdeltaC with sorcin indirectly modulates ryanodine receptor function in cardiac myocytes. J Mol Cell Cardiol. 2007;43:492-503 pubmed
    ..Since both proteins are capable of directly modulating RyR(2) activity, this interaction may serve as an additional or alternative indirect route by which both proteins can regulate RyR(2) opening status in cardiac myocytes. ..
  47. Hotta S, Morimura K, Ohya S, Muraki K, Takeshima H, Imaizumi Y. Ryanodine receptor type 2 deficiency changes excitation-contraction coupling and membrane potential in urinary bladder smooth muscle. J Physiol. 2007;582:489-506 pubmed
    The possibility that the ryanodine receptor type 2 (RyR2) can function as the major Ca(2+)-induced Ca(2+) release (CICR) channel in excitation-contraction (E-C) coupling was examined in smooth muscle cells (SMCs) isolated from urinary ..
  48. Xiao Z, Guo W, Yuen S, Wang R, Zhang L, Van Petegem F, et al. The H29D Mutation Does Not Enhance Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor. PLoS ONE. 2015;10:e0139058 pubmed publisher
    The N-terminal domain of the cardiac ryanodine receptor (RyR2) harbors a large number of naturally occurring mutations that are associated with stress-induced ventricular tachyarrhythmia and sudden death...
  49. George C, Rogers S, Bertrand B, Tunwell R, Thomas N, Steele D, et al. Alternative splicing of ryanodine receptors modulates cardiomyocyte Ca2+ signaling and susceptibility to apoptosis. Circ Res. 2007;100:874-83 pubmed
    Ca(2+) release via type 2 ryanodine receptors (RyR2) regulates cardiac function...
  50. Brunello L, Slabaugh J, Radwanski P, Ho H, Belevych A, Lou Q, et al. Decreased RyR2 refractoriness determines myocardial synchronization of aberrant Ca2+ release in a genetic model of arrhythmia. Proc Natl Acad Sci U S A. 2013;110:10312-7 pubmed publisher
    ..Our study reveals how aberrant DCR events can become synchronized in the intact myocardium, leading to triggered activity and the resultant DCs in the settings of a cardiac rhythm disorder. ..
  51. Brandenburg S, Kohl T, Williams G, Gusev K, Wagner E, Rog Zielinska E, et al. Axial tubule junctions control rapid calcium signaling in atria. J Clin Invest. 2016;126:3999-4015 pubmed publisher
    ..of voluminous axial tubules (ATs) with extensive junctions to the sarcoplasmic reticulum (SR) that include ryanodine receptor 2 (RyR2) clusters...
  52. Neco P, Torrente A, Mesirca P, Zorio E, Liu N, Priori S, et al. Paradoxical effect of increased diastolic Ca(2+) release and decreased sinoatrial node activity in a mouse model of catecholaminergic polymorphic ventricular tachycardia. Circulation. 2012;126:392-401 pubmed publisher
    ..Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored...
  53. Liu Q, Zheng Y, Korde A, Yadav V, Rathore R, Wess J, et al. Membrane depolarization causes a direct activation of G protein-coupled receptors leading to local Ca2+ release in smooth muscle. Proc Natl Acad Sci U S A. 2009;106:11418-23 pubmed publisher
    ..IP(3)), inducing initial Ca(2+) release through IP(3) receptors and then further Ca(2+) release via RyR2 due to a local Ca(2+)-induced Ca(2+) release process...
  54. Martins Marques T, Anjo S, Pereira P, Manadas B, Girão H. Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart. Mol Cell Proteomics. 2015;14:3040-55 pubmed publisher
    ..Data are available via ProteomeXchange with identifier PXD002331. ..
  55. Li N, Chiang D, Wang S, Wang Q, Sun L, Voigt N, et al. Ryanodine receptor-mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model. Circulation. 2014;129:1276-1285 pubmed publisher
    ..Abnormal sarcoplasmic reticulum (SR) Ca(2+) leak via the ryanodine receptor type 2 (RyR2) has been observed as a source of ectopic activity in various AF models...
  56. Min C, Yeom D, Lee K, Kwon H, Kang M, Kim Y, et al. Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca²+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart. Biochem J. 2012;447:371-9 pubmed publisher
    ..2-hybrid, glutathione transferase pull-down, co-immunoprecipitation and immunocytochemistry assays, we found that RyR2 (ryanodine receptor type 2), which is physically associated with VDAC2 (voltage-dependent anion channel 2), was co-..
  57. Marks A. Intracellular calcium-release channels: regulators of cell life and death. Am J Physiol. 1997;272:H597-605 pubmed
    ..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 ..
  58. Liu B, Ho H, Brunello L, Unudurthi S, Lou Q, Belevych A, et al. Ablation of HRC alleviates cardiac arrhythmia and improves abnormal Ca handling in CASQ2 knockout mice prone to CPVT. Cardiovasc Res. 2015;108:299-311 pubmed publisher
    ..suggest that rather than being functionally redundant, CASQ2 and HRC modulate cardiac ryanodine receptor-mediated (RyR2) Ca release in an opposing manner...
  59. Furtado M, Wilmanns J, Chandran A, Tonta M, Biben C, Eichenlaub M, et al. A novel conditional mouse model for Nkx2-5 reveals transcriptional regulation of cardiac ion channels. Differentiation. 2016;91:29-41 pubmed publisher
  60. Mu Y, Zhao W, Duan P, Chen Y, Zhao W, Wang Q, et al. RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes. PLoS ONE. 2014;9:e94905 pubmed publisher
    ..isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic ..
  61. Li M, Hothi S, Salvage S, Jeevaratnam K, Grace A, Huang C. Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity. Clin Exp Pharmacol Physiol. 2017;44:686-692 pubmed publisher
    Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels...
  62. Misumi D, Nagle D, McGrail S, Dussault B, Smutko J, Chen H, et al. The physical and genetic map surrounding the Lyst gene on mouse chromosome 13. Genomics. 1997;40:147-50 pubmed
    ..These data are consistent with LYST being the gene for the human Chediak-Higashi Syndrome and strengthen the synteny relationship between MMU13 and human 1q43. ..
  63. Wang R, Bolstad J, Kong H, Zhang L, Brown C, Chen S. The predicted TM10 transmembrane sequence of the cardiac Ca2+ release channel (ryanodine receptor) is crucial for channel activation and gating. J Biol Chem. 2004;279:3635-42 pubmed
    ..of mutations of each residue within the 24-amino acid TM10 sequence of the mouse cardiac ryanodine receptor (RyR2) on channel activation by caffeine and Ca(2+)...
  64. Kuwahara K, Saito Y, Takano M, Arai Y, Yasuno S, Nakagawa Y, et al. NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function. EMBO J. 2003;22:6310-21 pubmed
    ..Our results indicate NRSF to be a key transcriptional regulator of the fetal cardiac gene program and suggest an important role for NRSF in maintaining normal cardiac structure and function. ..
  65. Arnaiz Cot J, Damon B, Zhang X, Cleemann L, Yamaguchi N, Meissner G, et al. Cardiac calcium signalling pathologies associated with defective calmodulin regulation of type 2 ryanodine receptor. J Physiol. 2013;591:4287-99 pubmed publisher
    Cardiac ryanodine receptor (RyR2) is a homotetramer of 560 kDa polypeptides regulated by calmodulin (CaM), which decreases its open probability at diastolic and systolic Ca(2+) concentrations...
  66. Savoia C, Liu Q, Zheng Y, Yadav V, Zhang Z, Wu L, et al. Calcineurin upregulates local Ca(2+) signaling through ryanodine receptor-1 in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2014;307:L781-90 pubmed publisher
    ..However, their effects are not altered in RyR2(-/+) or RyR3(-/-) mouse ASMCs...
  67. Wang Q, Wang W, Wang G, Rodney G, Wehrens X. Crosstalk between RyR2 oxidation and phosphorylation contributes to cardiac dysfunction in mice with Duchenne muscular dystrophy. J Mol Cell Cardiol. 2015;89:177-84 pubmed publisher
    ..recent data suggesting the involvement of altered phosphorylation and oxidation of the cardiac ryanodine receptor (RyR2)/Ca(2+) release channel, we hypothesized that inhibition of RyR2 phosphorylation in a mouse model of DMD can ..
  68. Xiao B, Sutherland C, Walsh M, Chen S. Protein kinase A phosphorylation at serine-2808 of the cardiac Ca2+-release channel (ryanodine receptor) does not dissociate 12.6-kDa FK506-binding protein (FKBP12.6). Circ Res. 2004;94:487-95 pubmed
    Dissociation of FKBP12.6 from the cardiac Ca2+-release channel (RyR2) as a consequence of protein kinase A (PKA) hyperphosphorylation of RyR2 at a single amino acid residue, serine-2808, has been proposed as an important mechanism ..
  69. Aiba I, Wehrens X, Noebels J. Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death. Proc Natl Acad Sci U S A. 2016;113:E4895-903 pubmed publisher
    ..Genetic autopsies have detected "leaky" gain-of-function mutations in the ryanodine receptor-2 (RyR2) gene in both SUDEP and sudden cardiac death cases linked to catecholaminergic polymorphic ventricular tachycardia ..