Affinage

RYR2

Ryanodine receptor 2 · UniProt Q92736

Length
4967 aa
Mass
564.6 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RYR2 encodes the tetrameric cardiac sarcoplasmic reticulum (SR) Ca2+ release channel that mediates Ca2+-induced Ca2+ release during excitation-contraction coupling, and gain- and loss-of-function mutations distributed across its N-terminal, central, and C-terminal regions cause the inherited arrhythmias ARVD2/CPVT and CRDS (PMID:11159936, PMID:11157710, PMID:33825858). The channel is gated by cytosolic Ca2+ activation and Mg2+ inhibition together with luminal Ca2+, and its resting cytosolic Ca2+ sensitivity sets the luminal Ca2+ threshold for spontaneous store overload-induced Ca2+ release (SOICR) (PMID:25156119, PMID:35446340). CPVT-associated gain-of-function mutations sensitize the channel to luminal and/or cytosolic Ca2+ and lower this threshold, increasing arrhythmogenic spontaneous release, whereas loss-of-function mutations suppress Ca2+ activation, abolish SOICR, and produce a distinct CRDS phenotype that can include left ventricular non-compaction (PMID:16239587, PMID:23746327, PMID:37325910, PMID:31028179). Channel output is set by an integrated regulatory layer: calmodulin (CaM) binds RyR2 with high affinity at multiple Ca2+-dependent CaM-binding domains and inhibits the channel, and loss of CaM affinity—whether through disease, post-translational modification, or arrhythmogenic CaM mutations—elevates Ca2+ leak and arrhythmia (PMID:12614169, PMID:24186966, PMID:30530841, PMID:31230402). CaMKIIδ phosphorylation at S2814 drives a pathological conformational state with reduced CaM affinity and SR Ca2+ leak that underlies heart failure, atrial fibrillation, and catecholaminergic arrhythmia, while PKA phosphorylation at S2030 governs CaM-dependent inactivation, the Ca2+ release termination threshold, and Ca2+ alternans (PMID:22511749, PMID:22158709, PMID:27318036, PMID:33375811, PMID:36583384). Redox control adds a further axis: S-nitrosylation and cysteine oxidation render the channel leaky, ERp44 binding to luminal Cys4806 is redox-sensitive, and SR Ca2+ release feeds a mitochondrial ROS feedback loop that further oxidizes RyR2 (PMID:20080623, PMID:35086342, PMID:32444920, PMID:25106424). RyR2 function is additionally stabilized by integrin β1D and coupled to partner channels, including KCa3.1, SK2, and Cx43 hemichannels at membrane junctions (PMID:31461656, PMID:31841141, PMID:32122157, PMID:24747296). Beyond the heart, RyR2 shapes cardiomyocyte mitochondrial Ca2+ uptake and glucose oxidation (PMID:27621312), regulates pancreatic β-cell insulin secretion and survival via IRBIT and calpain-10 (PMID:25844899, PMID:15044459, PMID:35562179), drives hippocampal nuclear Ca2+ signaling for CREB-dependent transcription and synaptic strength (PMID:34389673, PMID:27482086), and activates Ca2+-AKT signaling that promotes CD8+ T cell exhaustion (PMID:38451948).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Establishing that RYR2 mutations cause inherited arrhythmia defined the gene as the disease-relevant cardiac SR Ca2+ release channel and located causal mutations across three structural regions.

    Evidence Genomic structure elucidation and mutation cosegregation analysis in ARVD2/CPVT families

    PMID:11157710 PMID:11159936

    Open questions at the time
    • Genetics alone did not reveal whether mutations gain or lose function
    • No biophysical mechanism for arrhythmia at the channel level
  2. 2002 Medium

    Quantifying mutation effects on FKBP12.6 binding offered an early candidate mechanism distinguishing arrhythmia-associated from ARVD2 mutations.

    Evidence Quantitative yeast two-hybrid assay of RyR2-FKBP12.6 interaction across mutations

    PMID:12459180

    Open questions at the time
    • Single binding method without channel functional readout
    • Later work found no FKBP12.6-RyR2 interaction change for several disease mutations
  3. 2003 High

    Defining how calmodulin inhibits RyR2 across all Ca2+ concentrations identified CaM as a key constitutive negative regulator and mapped the determinant to its C-terminal Ca2+-binding lobe.

    Evidence In vitro RyR2 activity assays with Ca2+-insensitive CaM mutants and ryanodine binding

    PMID:12614169

    Open questions at the time
    • Did not map the RyR2 CaM-binding domains involved
    • In vitro reconstitution did not establish in situ affinity or disease relevance
  4. 2005 High

    Resolving the channel-level defect of disease mutations showed enhanced luminal Ca2+ sensitivity and SOICR as the unifying gain-of-function mechanism, redirecting attention away from FKBP12.6.

    Evidence Inducible HEK293 RyR2 cell lines, single-channel recording, ryanodine binding, and Ca2+ imaging across six mutations

    PMID:16239587

    Open questions at the time
    • Did not resolve how N-terminal versus C-terminal mutations converge on the same gating change
    • Quantitative link to clinical onset not yet established
  5. 2013 High

    Linking an N-terminal CPVT mutation to reduced domain thermal stability and dual Ca2+ sensitization began to connect channel structure to SOICR dysregulation.

    Evidence Inducible HEK293 SOICR assay, single-channel recording, and thermal stability assay of recombinant N-terminal fragment

    PMID:23746327

    Open questions at the time
    • Full-length structural consequence not determined
    • Mechanism of inter-domain coupling to the pore unresolved
  6. 2011 High

    Phospho-site knock-in epistasis established CaMKII phosphorylation at S2814, not PKA at S2808, as the site required for SR Ca2+ leak, delayed afterdepolarizations, and atrial fibrillation.

    Evidence Double knock-in mice (FKBP12.6-/-:S2814A and :S2808A), confocal Ca2+ imaging, patch clamp, intracardiac pacing

    PMID:22158709

    Open questions at the time
    • Did not define the conformational change produced by S2814 phosphorylation
    • Upstream CaMKII isoform not yet isolated
  7. 2012 High

    Showing S2814 phosphorylation rises in heart failure and that S2814A mice resist pressure-overload extended the CaMKII-leak mechanism to acquired cardiac disease.

    Evidence S2814A knock-in mice, transverse aortic constriction, Ca2+ imaging, and human non-ischemic HF tissue

    PMID:22511749

    Open questions at the time
    • Did not separate RyR2 leak from other CaMKII substrate contributions to HF
    • Therapeutic targeting not addressed
  8. 2013 High

    Measuring CaM-RyR2 affinity in situ established that most Z-line CaM is RyR2-bound and that reduced affinity drives Ca2+ waves and stress arrhythmia, making CaM binding a functional disease axis.

    Evidence FRET in permeabilized cardiomyocytes, RyR2(ADA/+) knock-in mice, and post-MI rat HF model

    PMID:24186966

    Open questions at the time
    • Did not identify what lowers CaM affinity in disease at the molecular level
    • Number and identity of CaM-binding domains not resolved
  9. 2014 High

    Defining the cytosolic/luminal Ca2+ and Mg2+ sensitivities of native human RyR2 and the SK2 functional coupling characterized the channel's intrinsic gating and an output partner.

    Evidence Single-channel bilayer recordings of native human/sheep/rat RyR2; co-IP and patch clamp for SK2 coupling

    PMID:24747296 PMID:25156119

    Open questions at the time
    • Species differences in luminal sensitivity mechanistically unexplained
    • SK2 co-IP from single lab without structural interface
  10. 2015 High

    Genetic dissection of CaMKIIδ and the discovery of β-cell and metabolic roles broadened RyR2 leak beyond contraction to chronic catecholamine cardiomyopathy and extracardiac biology.

    Evidence CaMKIIδ-KO and S2814A mice with chronic isoproterenol; transgenic CPVT mice and human islet Ca2+/ER stress assays

    PMID:25844899 PMID:26080362

    Open questions at the time
    • Tissue-specific regulation of RyR2 leak in islets versus heart not unified
    • Did not establish the β-cell RyR2 interactome
  11. 2016 High

    Connecting S2814 phosphorylation to a defined pathological conformation (increased DPc10 access, reduced CaM affinity) and dantrolene rescue mechanistically unified phosphorylation, CaM regulation, and leak; parallel work defined neuronal RyR2 roles in synapses, cardiac mitochondrial metabolism, and β-cell survival.

    Evidence S2814D/A knock-in mice, DPc10 conformational and FRET CaM assays; RyR2-R176Q neuronal knock-in; cardiac Ryr2 haploinsufficient mice; β-cell calpain-10 apoptosis assays

    PMID:15044459 PMID:27318036 PMID:27482086 PMID:27621312

    Open questions at the time
    • Structural basis of the DPc10-accessible state not solved
    • Extracardiac mechanisms each rest on individual models
  12. 2019 High

    Mapping four Ca2+-dependent CaM-binding domains and showing phosphorylation gates CaM inhibition in human RyR2 resolved how CaM senses Ca2+ and integrates phosphorylation state to control the channel.

    Evidence Fluorescence anisotropy of CaMBD peptides; single-channel bilayer and FRET with phosphomimetic knock-in RyR2; systematic study of 14 arrhythmogenic CaM mutations

    PMID:30530841 PMID:30928430 PMID:31230402

    Open questions at the time
    • How phosphorylation alters CaMBD-CaM contacts structurally unresolved
    • Integration of the four CaMBDs in the intact tetramer not visualized
  13. 2020 High

    PKA-S2030 control of CaM-dependent inactivation and Ca2+ alternans, an integrin β1D-RyR2 stabilizing interaction, a mitochondrial ROS feedback loop, RyR2-Cx43 hemichannel coupling, and RyR2 inhibition as flecainide's antiarrhythmic mechanism collectively expanded the regulatory and pharmacological map.

    Evidence In vivo CaM-variant delivery and Ca2+ imaging; integrin β1D bilayer reconstitution and KO mice; genetic ROS/Ca2+ probes with dominant-negative MCU; PLA/co-IP and Ca2+-clamp for Cx43; matched flecainide analogues across bilayer, sodium-channel, and in vivo CPVT assays

    PMID:31841141 PMID:32122157 PMID:32444920 PMID:33297863 PMID:33375811

    Open questions at the time
    • Spatial relationship between S2030 and S2814 phospho-control not unified
    • Integrin and Cx43 interaction interfaces not structurally defined
  14. 2021 High

    Identifying loss-of-function mutations causing a CRDS distinct from CPVT, plus neuronal nuclear Ca2+ signaling roles, established the bidirectional disease spectrum and CNS reach of RyR2.

    Evidence Bilayer single-channel and SOICR/dominant-negative studies of E4146K/G4935R; pharmacological RyR inhibition with CREB/Npas4 readouts in hippocampal neurons

    PMID:33825858 PMID:34389673

    Open questions at the time
    • In vivo cardiac phenotype of these LOF mutations not yet shown at this stage
    • Neuronal nuclear Ca2+ link rests on pharmacology without genetic RyR2 ablation
  15. 2022 High

    Defining resting cytosolic activity (Arest) as the determinant of the luminal Ca2+ threshold and correlating it with patient onset age, plus the redox-sensitive ERp44-Cys4806 interaction, provided quantitative and molecular bases for arrhythmogenesis.

    Evidence HEK293 cytosolic/ER Ca2+ measurements with kinetic modeling across CPVT mutations; co-IP, C4806 mutagenesis, molecular dynamics, and ROS biosensor for ERp44/Ero1α

    PMID:35086342 PMID:35446340

    Open questions at the time
    • Arest framework derived in HEK293, not native myocytes
    • Structural docking of ERp44 on the luminal face not resolved
  16. 2023 High

    Genetic RyR2 depletion linking ER stress/ATF4 signaling to cardiomyocyte maturation, and an LOF I4855M knock-in producing LVNC, connected RyR2 channel function to development and structural cardiomyopathy.

    Evidence Cas9/AAV9 somatic RYR2 knockout with RNA-Seq/ChIP-Seq and ATF4 manipulation; I4855M knock-in mice with echocardiography and Ca2+ imaging

    PMID:35576474 PMID:37325910

    Open questions at the time
    • How channel activity is transduced to ATF4/ER stress not mechanistically traced
    • Developmental versus adult contributions of RyR2 not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the regulatory inputs (CaM occupancy, S2814/S2030 phosphorylation, redox modifications, ERp44 and integrin β1D binding) are spatially integrated within the intact tetramer to set open probability, and how tissue-specific interactomes redirect RyR2 output in neurons, β cells, and T cells, remain unresolved.
  • No unified structural model integrating phospho-, CaM-, and redox-control sites
  • Extracardiac RyR2 partner complexes not fully reconstituted
  • Causal link between channel conformational states and downstream transcription/metabolism incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1430728 Metabolism 2 R-HSA-162582 Signal Transduction 2 R-HSA-397014 Muscle contraction 2
Partners
CALM1ERP44FKBP12.6GJA1 (CX43)IRBITITGB1 (INTEGRIN Β1D)JPH3KCNN2 (SK2)
Complex memberships
Cav1.3-RyR2-KCa3.1 junctional complexRyR2-calmodulin complexRyR2-calstabin2 (FKBP12.6) complex

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 RYR2 mutations (in N-terminal, central, and C-terminal regions) cause ARVD2/CPVT; RyR2 encodes the cardiac sarcoplasmic reticulum Ca2+ release channel that mediates Ca2+-induced Ca2+ release during excitation-contraction coupling. Genomic structure elucidation, mutation identification by sequencing in affected families, cosegregation analysis Human molecular genetics High 11157710 11159936
2005 Disease-linked RyR2 mutations (from N-terminal, central, and C-terminal regions) enhance the sensitivity of the channel to luminal (but not cytosolic) Ca2+ activation and increase the propensity for store overload-induced Ca2+ release (SOICR); no alteration in FKBP12.6-RyR2 interaction was detected. Stable inducible HEK293 cell lines expressing mutant RyR2, single-channel analysis, [3H]ryanodine binding, single-cell Ca2+ imaging in HL-1 cardiac cells Circulation research High 16239587
2002 VTSIP-associated RyR2 point mutations increase, while ARVD2-associated mutations decrease, binding of RyR2 to its gating protein FKBP12.6, as measured by quantitative yeast two-hybrid assay. Quantitative yeast two-hybrid assay Biochemical and biophysical research communications Medium 12459180
2010 In the mdx mouse model of Duchenne muscular dystrophy, RyR2 is S-nitrosylated and depleted of calstabin2 (FKBP12.6), resulting in leaky RyR2 channels and diastolic SR Ca2+ leak that triggers cardiac arrhythmias; stabilizing the RyR2-calstabin2 complex with S107 inhibited SR Ca2+ leak and prevented arrhythmias in vivo. Co-immunoprecipitation, S-nitrosylation assay, confocal Ca2+ imaging, in vivo arrhythmia monitoring in mdx mice Proceedings of the National Academy of Sciences of the United States of America High 20080623
2012 CaMKII phosphorylation of RyR2 at S2814 (but not PKA phosphorylation at S2808) is increased in non-ischemic heart failure; knock-in mice with inactivated S2814 (S2814A) are protected from pressure-overload heart failure and exhibit reduced SR Ca2+ leak. Knock-in mouse model (S2814A), transverse aortic constriction, confocal Ca2+ imaging, Western blotting Circulation research High 22511749
2011 CaMKII phosphorylation of RyR2 at S2814 (not S2808) is required for SR Ca2+ leak, delayed afterdepolarizations (DADs), and atrial fibrillation induction in FKBP12.6-knockout mice; genetic inhibition of S2814 phosphorylation (S2814A knock-in) reduces Ca2+ spark frequency and prevents AF. Double knock-in mouse models (FKBP12.6-/-:S2814A and FKBP12.6-/-:S2808A), confocal Ca2+ imaging, patch clamp, intracardiac pacing Circulation research High 22158709
2003 CaM inhibits RyR2 at all Ca2+ concentrations (100 nM–1 mM), increasing the Ca2+ EC50 of RyR2 7–10-fold; C-terminal Ca2+-binding sites on CaM determine the inhibitory effect, and apoCaM (Ca2+-binding deficient mutant) activates RyR2 and acts as a competitive inhibitor of Ca2+CaM regulation. Biochemical assay of RyR2 activity with Ca2+-insensitive CaM mutants, [3H]ryanodine binding Biochemistry High 12614169
2013 In situ, CaM binds RyR2 with high affinity (Kd ~10–20 nM); >90% of Z-line CaM in cardiomyocytes is RyR2-bound; reduced CaM-RyR2 affinity (~3-fold increase in Kd) occurs in post-MI rat heart failure; reduced CaM binding in RyR2(ADA/+) knock-in mice increases Ca2+ wave production and stress-induced ventricular arrhythmia. FRET in permeabilized cardiomyocytes, RyR2(ADA/+) knock-in mouse model, post-MI rat heart failure model Circulation research High 24186966
2016 CaMKII phosphorylation of RyR2 at S2814 promotes a pathological RyR2 conformational state (increased DPc10 access, reduced CaM affinity, elevated Ca2+ leak); dantrolene restores CaM affinity, reduces DPc10 access, and suppresses SR Ca2+ leak and ventricular tachycardia in RyR2-S2814D mice. Phosphomimetic/phosphoablative knock-in mice (S2814D/S2814A), DPc10 peptide conformational assay, FRET-based CaM affinity measurement, confocal Ca2+ imaging, in vivo arrhythmia assessment Journal of molecular and cellular cardiology High 27318036
2015 CaMKIIδ-dependent phosphorylation of RyR2-S2814 mediates SR Ca2+ leak in response to β-adrenergic stimulation; CaMKIIδ-KO and S2814A knock-in mice are protected from cardiomyopathy induced by chronic isoproterenol, without blocking hypertrophy. CaMKIIδ-KO and S2814A knock-in mice, Langendorff heart perfusion, confocal Ca2+ imaging, chronic isoproterenol treatment Journal of molecular and cellular cardiology High 26080362
2019 CaM binds to four CaM-binding domains (CaMBD1a, -1b, -2, -3) in RyR2 in a Ca2+-dependent manner; the CaM C-domain anchors to CaMBD2 (essentially Ca2+-saturated at rest), while the CaM N-domain dynamically senses Ca2+ in the physiological range when complexed with CaMBD2 or CaMBD3. Fluorescence anisotropy with TAMRA-labeled CaMBD peptides, Ca2+ titrations, isolated CaM domain binding experiments The Biochemical journal High 30530841
2019 Phosphorylation of human RyR2 at S2808 or S2814 is necessary and sufficient for CaM inhibitory activity on RyR2; CaM (100 nM) inhibits RyR2 from failing human hearts (~50%) but has no effect on RyR2 from healthy human hearts, a difference attributable to phosphorylation state. Artificial lipid bilayer single-channel recording, FRET (donor-FKBP12.6/acceptor-CaM), Ca2+ spark measurements in phosphomimetic/phosphoablated RyR2 knock-in cardiomyocytes Journal of molecular and cellular cardiology High 30928430
2020 Ca2+-CaM dependent inactivation of RyR2 is a major determinant of Ca2+ alternans; CaM gain-of-function (CaM-M37Q) promotes and CaM loss-of-function (CaM-1-4) suppresses Ca2+ alternans in intact working mouse hearts; PKA phosphorylation of RyR2 at S2030 modulates CaM-dependent inactivation and Ca2+ alternans. In vivo adenoviral delivery of CaM variants into mouse myocardium, confocal Ca2+ imaging in Langendorff-perfused hearts, numerical modeling Circulation research High 33375811
2022 PKA phosphorylation of RyR2 at S2030 governs Ca2+ release termination threshold via CaM-dependent inactivation; S2030L mutation abolishes CaM-wild-type and PKA effects on termination but preserves CaMKII effects, placing S2030 within the CaM-dependent inactivation pathway. ER Ca2+ imaging in HEK293 cells, S2030L knock-in mouse model, confocal Ca2+ imaging, pharmacological CaMKII/PKA inhibition Circulation research High 36583384
2020 RyR2 channel inhibition (not solely sodium channel block) is the principal mechanism of flecainide's antiarrhythmic action in CPVT; N-methylated flecainide analogues that lose RyR2 inhibitory potency (while retaining sodium channel block) fail to suppress CPVT arrhythmias in Casq2-/- mice. Synthesis of N-methylated flecainide analogues, lipid bilayer RyR2 single-channel recordings, HEK293 sodium channel assays, membrane-permeabilized and voltage-clamped Casq2-/- cardiomyocytes, in vivo catecholamine challenge Circulation research High 33297863
2013 The CPVT-associated RyR2 G230C N-terminal mutation enhances SOICR propensity by sensitizing the channel to both luminal and cytosolic Ca2+ activation, and decreases thermal stability of the N-terminal domain (residues 1–547) of RyR2. Stable inducible HEK293 cell lines, single-cell Ca2+ imaging (SOICR assay), single-channel recordings, [3H]ryanodine binding, thermal stability assay of recombinant N-terminal fragment The Biochemical journal High 23746327
2015 RyR2 in pancreatic β cells regulates insulin secretion and glucose homeostasis; leaky RyR2 channels (via oxidation and S-nitrosylation) cause ER stress, mitochondrial dysfunction, and decreased insulin release in CPVT mice and diabetic human islets. Transgenic CPVT RyR2 mice, islet isolation and Ca2+ imaging, ER stress assays, mitochondrial function assays, pharmacological Ca2+ leak inhibition The Journal of clinical investigation High 25844899
2004 Inhibiting RyR2 in pancreatic β cells markedly increases apoptosis via a caspase-3-independent, calpain-10-dependent death pathway; RyR2 activity suppresses calpain-10-mediated apoptosis in β cells. Pharmacological inhibition (ryanodine), pharmacological and genetic inhibition of calpain-10 in human and mouse β cells, apoptosis assays The Journal of biological chemistry High 15044459
2016 RyR2 Ca2+ release in cardiomyocytes specifically promotes mitochondrial Ca2+ uptake and glucose oxidation via pyruvate dehydrogenase activation; 50% reduction in Ryr2 protein (haploinsufficiency) decreases mitochondrial Ca2+ signals and impairs glucose oxidation without affecting cardiac contraction. Inducible heart-specific Ryr2 haploinsufficient mice (cRyr2Δ50), confocal Ca2+ imaging, metabolic flux analysis, metabolomics, proteomics, transcriptomics The Journal of biological chemistry High 27621312
2022 ERp44 associates with RyR2 via intraluminal cysteine 4806 in a redox-sensitive manner; Ero1α-mediated SR oxidation causes ERp44 dissociation from the RyR2 complex, increasing RyR2 Ca2+ channel activity and promoting proarrhythmic spontaneous Ca2+ release. Co-immunoprecipitation, site-directed mutagenesis (C4806), molecular dynamics simulation, genetic Ero1α overexpression/knockdown, intra-SR ROS biosensor (ERroGFP), pharmacological inhibition (EN460), rat TAB model Circulation research High 35086342
2019 Junctophilin proteins (JPH3/JPH4) tether a Cav1.3-RyR2-KCa3.1 tripartite complex at the plasma membrane-ER junction in hippocampal CA1 neurons; disruption of this complex (by JPH3/4 shRNA or antibody infusion) dissociates Cav1.3-RyR2-KCa3.1 and reduces the slow AHP current. dSTORM super-resolution microscopy, FRET microscopy, shRNA knockdown, antibody infusion, patch clamp electrophysiology in CA1 neurons Cell reports High 31461656
2021 RyR2 physically interacts with Cx43 (<40 nm proximity by PLA); RyR activation and intracellular Ca2+ elevation together are necessary to open Cx43 hemichannels at diastolic membrane potential; a RyR-mimicking peptide (RyRHCIp) inhibits RyR/Ca2+-triggered HC activation. Proximity ligation assay, co-immunoprecipitation, whole-cell patch clamp, molecular modelling, Ca2+ clamp experiments Cardiovascular research High 31841141
2020 Augmented RyR2 activity (pharmacological or genetic CPVT mutation) increases mitochondrial ROS emission via altered SR-mitochondrial Ca2+ transfer; mito-ROS in turn oxidizes RyR2, further amplifying proarrhythmic SR Ca2+ release in a positive feedback cycle (leak begets leak); dominant-negative MCU abrogates this effect. Spatially restricted genetic ROS probes, mitochondrial Ca2+ probe (mtRCamp1h), dominant-negative MCU expression, CPVT mouse ventricular myocytes, pharmacological ROS scavenging Basic research in cardiology High 32444920
2020 A single RyR2 point mutation E4872Q that reduces RyR2 open time prevents neuronal hyperexcitability, memory impairment, dendritic spine loss, and neuronal cell death in 5xFAD Alzheimer's disease mice; the mechanism involves upregulation of hippocampal CA1 A-type K+ current. RyR2-E4872Q knock-in mouse crossed with 5xFAD, behavioral tests, patch clamp (A-type K+ current), pharmacological treatment (R-carvedilol) Cell reports High 32966798
2016 The leaky RyR2-R176Q gain-of-function mutation in neurons selectively strengthens excitatory (but not inhibitory) synapses and lowers the threshold for spreading depolarization in the dorsal medulla, leading to cardiorespiratory collapse; this links neuronal RyR2 Ca2+ dysregulation to brainstem spreading depolarization as a mechanism of sudden death. RyR2-R176Q knock-in mouse model (RQ/+), in vitro electrophysiology (excitatory/inhibitory synapse recordings), spreading depolarization assay, in vivo EEG/ECG monitoring Proceedings of the National Academy of Sciences of the United States of America High 27482086
2016 A RyR2 loss-of-function mutation (I4855M) in the inner vestibule of the pore inhibits caffeine-induced Ca2+ release and exerts a dominant-negative effect on wild-type RyR2 when co-expressed in HEK293 cells. HEK293 cell Ca2+ release assay, homology modelling of RyR2 pore region, co-expression studies Journal of electrocardiology Medium 27646203
2021 Two additional RyR2 loss-of-function mutations (E4146K and G4935R) markedly suppress cytosolic and luminal Ca2+ activation of single RyR2 channels; G4935R exerts a dominant-negative effect on wild-type RyR2; these LOF mutations are associated with a distinct arrhythmia syndrome (CRDS) different from CPVT. HEK293 cell SOICR assay, [3H]ryanodine binding, single-channel recordings in lipid bilayers, co-expression dominant-negative studies Bioscience reports High 33825858
2020 Integrin β1D protein directly stabilizes RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time (lipid bilayer patch clamp); loss of integrin β1D in ARVC leads to RyR2-S2030 hyperphosphorylation and aberrant Ca2+ handling causing catecholamine-sensitive polymorphic ventricular tachycardia. Purified integrin β1D protein + lipid bilayer patch clamp single-channel recordings, cardiac-specific β1D KO mouse model, Western blotting, confocal Ca2+ imaging Circulation High 32122157
2014 Doxorubicin and its metabolite doxorubicinol bind to and activate single RyR2 channels, then cause irreversible inhibition via thiol oxidation (reducing thiol groups on RyR2); both effects are reversed/prevented by the reducing agent DTT, identifying oxidation of RyR2 cysteines as the mechanism of secondary inhibition. Single RyR2 channel recordings, thiol group quantification, SR vesicle Ca2+ uptake assay, drug washout experiments Molecular pharmacology High 25106424
2019 All 14 arrhythmogenic CaM mutations tested diminish CaM-dependent inhibition of RyR2-mediated Ca2+ release and increase SOICR; many CaM mutations fail to inhibit or even facilitate RyR2-mediated Ca2+ release at elevated cytosolic Ca2+, and alter Ca2+-dependency of CaM binding to the RyR2 CaM-binding domain. HEK293 cells expressing RyR2 with arrhythmogenic CaM mutations, SOICR Ca2+ imaging, permeabilized cell Ca2+ release assay, CaM-binding domain interaction studies The FEBS journal High 31230402
2014 Human RyR2 displays cytoplasmic Ca2+ activation (Ka ~4 µM) inhibited by cytoplasmic Mg2+ (Ki ~10 µM); luminal Ca2+ activation (Ka ~35 µM) is similar to sheep but distinct from rat; physiological Mg2+ (1 mM) raises Ka for cytoplasmic Ca2+ to ~30 µM in human and sheep RyR2. Artificial lipid bilayer single-channel recordings of native RyR2 from healthy and failing human, sheep, and rat hearts The Journal of general physiology High 25156119
2014 RyR2-mediated Ca2+ release is necessary and sufficient for activation of SK2 (small-conductance Ca2+-activated K+) channels in atrial cardiomyocytes; SK2 and RyR2 co-immunoprecipitate from native cardiac tissue, indicating a physical interaction. Whole-cell patch clamp, co-immunoprecipitation, lentiviral shRNA knockdown of RyR2, pharmacological RyR2 activation/inhibition, confocal Ca2+ imaging PloS one Medium 24747296
2022 Cytosolic Ca2+-dependent activity of RyR2 at resting Ca2+ (Arest) is the primary determinant of the ER luminal Ca2+ threshold for spontaneous Ca2+ release; CPVT mutations increase Arest and lower the threshold [Ca2+]ER in a manner that correlates with age of disease onset in patients. HEK293 cell expression of WT and CPVT-mutant RYR2, fluorescent Ca2+ indicators for cytosolic and ER Ca2+, in silico modeling The Journal of general physiology High 35446340
2023 RyR2 depletion in cardiomyocytes activates ER stress pathways (including ATF4 upregulation) that perturb cardiomyocyte maturation; tauroursodeoxycholic acid (ER stress alleviator) partially rescues these defects; ATF4 overexpression recapitulates RyR2-depletion phenotype, with protein biosynthesis genes as major ATF4 targets. Cas9/AAV9 somatic RYR2 knockout in cardiomyocytes, genetic mosaic analysis, RNA-Seq, bioChIP-Seq, tauroursodeoxycholic acid treatment, ATF4 overexpression Cardiovascular research High 35576474
2021 RyR2-mediated Ca2+ release in hippocampal neurons contributes to nuclear Ca2+ signals generated by neuronal activity; RyR-mediated Ca2+ release is required for CREB phosphorylation, Npas4 expression, and RyR2 upregulation in response to gabazine or high-frequency stimulation. Confocal Ca2+ imaging in primary hippocampal neurons, pharmacological RyR inhibition with ryanodine, glutamate uncaging, high-frequency field stimulation, Western blot Proceedings of the National Academy of Sciences of the United States of America Medium 34389673
2023 RyR2 loss-of-function mutation I4855M increases Ca2+-induced Ca2+ release gain, abolishes SOICR, elevates SR Ca2+ load, prolongs Ca2+ transient decay, and elevates end-diastolic Ca2+ upon rapid pacing, providing a mechanism for CRDS-associated LVNC. I4855M knock-in mouse model, echocardiography, confocal Ca2+ imaging, immunoblotting, histological analysis Circulation research High 37325910
2020 In ARVC hearts, integrin β1D deficiency leads to RyR2-S2030 hyperphosphorylation through a DSP-loss → ERK1/2-fibronectin-ubiquitin/lysosome pathway, causing RyR2 dysfunction and catecholamine-sensitive ventricular tachycardia. Protein mass spectrometry of ARVC hearts, cardiac-specific β1D KO mouse, Western blotting, confocal Ca2+ imaging Circulation Medium 32122157
2019 KN93, widely used as a CaMKII inhibitor, directly binds CaM and disrupts high-affinity CaM-NaV1.5 interaction and alters NaV1.5 channel function; KN93 also increases RyR2 Ca2+ release in cardiomyocytes independently of CaMKII, by interfering with CaM binding to RyR2. X-ray crystallography (CaM-KN93 structure), NMR spectroscopy, stopped-flow kinetics, NaV1.5 functional assay, confocal Ca2+ imaging in cardiomyocytes Cell calcium High 31401388
2020 CD38 expression on CD8+ T cells elevates intracellular Ca2+ through RyR2 Ca2+ channel activation, promoting chronic AKT activation and TCF1 loss leading to terminal CD8+ T cell exhaustion; RyR2 knockdown in CD8+ T cells maintains TCF1 levels and improves anti-tumor responses and responsiveness to anti-PD1 therapy. Genetic ablation of CD38, RyR2 knockdown in CD8+ T cells, Ca2+ imaging, AKT inhibition, single-cell RNA sequencing, in vivo tumor models Proceedings of the National Academy of Sciences of the United States of America Medium 38451948
2022 RyR2 deletion from INS-1 β cells (RyR2KO) reduces IRBIT protein levels, increases IP3R activity, reduces insulin content, impairs insulin secretion, reduces INS1 and INS2 mRNA, and increases nuclear AHCY with increased exonic DNA methylation; RyR2 and IRBIT co-regulate insulin gene expression and secretion. CRISPR knockout of RyR2 in INS-1 cells, IRBIT KO, insulin secretion assays, RT-PCR, DNA methylation analysis, exploratory proteomics Scientific reports Medium 35562179
2018 RyR2-P2328S mutation from arrhythmic RyR2S/S mice shifts Ca2+ activation 10-fold (AC50 from ~3.5 µM to ~320 nM) and dramatically shifts Ca2+ inactivation threshold >1000-fold (IC50 from ~50 mM to ≤7 µM, within systolic Ca2+ range), without changes in phosphorylation or FKBP12 binding. Artificial lipid bilayer single-channel recordings from RyR2S/S mouse hearts, Western blotting for phosphorylation and FKBP binding Journal of cell science High 31028179
2022 RyR2 clusters in the periphery of live ventricular myocytes show irregular distribution and dynamic movement (detected by GFP-tagged RyR2 knock-in), unlike the ordered arrays in the interior; peripheral cluster movement is modulated by external Ca2+ and RyR2 activators/inhibitors, and peripheral clusters generate Ca2+ release similar to interior clusters. GFP-RyR2 knock-in mouse model, confocal imaging, TIRF microscopy, simultaneous Ca2+/GFP imaging in live ventricular myocytes and intact hearts Biophysical journal High 29401432

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2). Human molecular genetics 585 11159936
2001 Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 558 11157710
2005 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. Circulation research 286 16239587
2009 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 mutational analysis. Journal of the American College of Cardiology 267 19926015
2010 Leaky RyR2 trigger ventricular arrhythmias in Duchenne muscular dystrophy. Proceedings of the National Academy of Sciences of the United States of America 208 20080623
2012 Role of RyR2 phosphorylation at S2814 during heart failure progression. Circulation research 178 22511749
2015 Calcium release channel RyR2 regulates insulin release and glucose homeostasis. The Journal of clinical investigation 167 25844899
2014 Role of RyR2 phosphorylation in heart failure and arrhythmias: Controversies around ryanodine receptor phosphorylation in cardiac disease. Circulation research 163 24723656
1995 A new locus for arrhythmogenic right ventricular cardiomyopathy (ARVD2) maps to chromosome 1q42-q43. Human molecular genetics 154 8589694
2011 Inhibition of CaMKII phosphorylation of RyR2 prevents induction of atrial fibrillation in FKBP12.6 knockout mice. Circulation research 134 22158709
2014 Adverse effects of doxorubicin and its metabolic product on cardiac RyR2 and SERCA2A. Molecular pharmacology 121 25106424
2004 RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets. The Journal of biological chemistry 111 15044459
2005 Spectrum and prevalence of cardiac ryanodine receptor (RyR2) mutations in a cohort of unrelated patients referred explicitly for long QT syndrome genetic testing. Heart rhythm 110 16188589
2020 Increased RyR2 activity is exacerbated by calcium leak-induced mitochondrial ROS. Basic research in cardiology 109 32444920
2010 Calmodulin kinase II inhibition prevents arrhythmias in RyR2(R4496C+/-) mice with catecholaminergic polymorphic ventricular tachycardia. Journal of molecular and cellular cardiology 100 20937285
2016 CaMKII-dependent phosphorylation of RyR2 promotes targetable pathological RyR2 conformational shift. Journal of molecular and cellular cardiology 97 27318036
2017 Allele-Specific Silencing of Mutant mRNA Rescues Ultrastructural and Arrhythmic Phenotype in Mice Carriers of the R4496C Mutation in the Ryanodine Receptor Gene (RYR2). Circulation research 82 28620067
2020 RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT. Circulation research 81 33297863
2018 In Vivo Ryr2 Editing Corrects Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation research 78 30355031
2013 Cardiac myocyte Z-line calmodulin is mainly RyR2-bound, and reduction is arrhythmogenic and occurs in heart failure. Circulation research 69 24186966
2014 Role of RyR2 phosphorylation in heart failure and arrhythmias: protein kinase A-mediated hyperphosphorylation of the ryanodine receptor at serine 2808 does not alter cardiac contractility or cause heart failure and arrhythmias. Circulation research 67 24723657
2015 CaMKIIδ mediates β-adrenergic effects on RyR2 phosphorylation and SR Ca(2+) leak and the pathophysiological response to chronic β-adrenergic stimulation. Journal of molecular and cellular cardiology 66 26080362
2013 'Ryanopathy': causes and manifestations of RyR2 dysfunction in heart failure. Cardiovascular research 65 23408344
2019 Junctophilin Proteins Tether a Cav1-RyR2-KCa3.1 Tripartite Complex to Regulate Neuronal Excitability. Cell reports 57 31461656
2014 Prevalence and significance of rare RYR2 variants in arrhythmogenic right ventricular cardiomyopathy/dysplasia: results of a systematic screening. Heart rhythm 55 25041964
2023 RYR2-ryanodinopathies: from calcium overload to calcium deficiency. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 54 37387319
2003 Regulation of the RYR1 and RYR2 Ca2+ release channel isoforms by Ca2+-insensitive mutants of calmodulin. Biochemistry 54 12614169
2016 Leaky RyR2 channels unleash a brainstem spreading depolarization mechanism of sudden cardiac death. Proceedings of the National Academy of Sciences of the United States of America 53 27482086
1997 Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and pregnant human myometrium. The Biochemical journal 50 9148749
2020 Limiting RyR2 Open Time Prevents Alzheimer's Disease-Related Neuronal Hyperactivity and Memory Loss but Not β-Amyloid Accumulation. Cell reports 49 32966798
2021 RyR2 and Calcium Release in Heart Failure. Frontiers in physiology 48 34690808
2016 A novel RYR2 loss-of-function mutation (I4855M) is associated with left ventricular non-compaction and atypical catecholaminergic polymorphic ventricular tachycardia. Journal of electrocardiology 47 27646203
2013 Loss of Nav1.5 expression and function in murine atria containing the RyR2-P2328S gain-of-function mutation. Cardiovascular research 47 23723061
2020 Integrin β1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation 45 32122157
2019 The CaMKII inhibitor KN93-calmodulin interaction and implications for calmodulin tuning of NaV1.5 and RyR2 function. Cell calcium 44 31401388
2019 LncRNA-LINC00472 contributes to the pathogenesis of atrial fibrillation (Af) by reducing expression of JP2 and RyR2 via miR-24. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 41 31562981
2008 Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts. Acta physiologica (Oxford, England) 41 18419777
2002 The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations. Biochemical and biophysical research communications 40 12459180
2021 RyR2 regulates Cx43 hemichannel intracellular Ca2+-dependent activation in cardiomyocytes. Cardiovascular research 36 31841141
2021 Identification of loss-of-function RyR2 mutations associated with idiopathic ventricular fibrillation and sudden death. Bioscience reports 35 33825858
2021 Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations: Clinical Phenotypes and In Vitro Characterization. Circulation. Arrhythmia and electrophysiology 33 34546788
2022 Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia. Circulation research 32 35086342
2020 Rieske iron-sulfur protein induces FKBP12.6/RyR2 complex remodeling and subsequent pulmonary hypertension through NF-κB/cyclin D1 pathway. Nature communications 32 32669538
2019 Ca2+-dependent calmodulin binding to cardiac ryanodine receptor (RyR2) calmodulin-binding domains. The Biochemical journal 32 30530841
2017 The emerging role of calmodulin regulation of RyR2 in controlling heart rhythm, the progression of heart failure and the antiarrhythmic action of dantrolene. Clinical and experimental pharmacology & physiology 32 27626620
2022 Molecular, Subcellular, and Arrhythmogenic Mechanisms in Genetic RyR2 Disease. Biomolecules 31 35892340
2019 Ryanodine receptor 2 (RYR2) mutation: A potentially novel neurocardiac calcium channelopathy manifesting as primary generalised epilepsy. Seizure 31 30849713
2018 CRISPR/Cas9 Gene editing of RyR2 in human stem cell-derived cardiomyocytes provides a novel approach in investigating dysfunctional Ca2+ signaling. Cell calcium 30 29730419
2023 The selective RyR2 inhibitor ent-verticilide suppresses atrial fibrillation susceptibility caused by Pitx2 deficiency. Journal of molecular and cellular cardiology 29 37080450
2020 Classification and correlation of RYR2 missense variants in individuals with catecholaminergic polymorphic ventricular tachycardia reveals phenotypic relationships. Journal of human genetics 29 32152366
2015 Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts. Acta physiologica (Oxford, England) 29 25850710
2020 Ca2+-CaM Dependent Inactivation of RyR2 Underlies Ca2+ Alternans in Intact Heart. Circulation research 28 33375811
2016 Cardiac Ryanodine Receptor (Ryr2)-mediated Calcium Signals Specifically Promote Glucose Oxidation via Pyruvate Dehydrogenase. The Journal of biological chemistry 28 27621312
2015 The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles. Pflugers Archiv : European journal of physiology 28 26545784
2015 Crosstalk between RyR2 oxidation and phosphorylation contributes to cardiac dysfunction in mice with Duchenne muscular dystrophy. Journal of molecular and cellular cardiology 28 26555638
2021 RyR-mediated Ca2+ release elicited by neuronal activity induces nuclear Ca2+ signals, CREB phosphorylation, and Npas4/RyR2 expression. Proceedings of the National Academy of Sciences of the United States of America 27 34389673
2021 Provocation Testing and Therapeutic Response in a Newly Described Channelopathy: RyR2 Calcium Release Deficiency Syndrome. Circulation. Genomic and precision medicine 27 34949103
2014 Long-term simulated microgravity causes cardiac RyR2 phosphorylation and arrhythmias in mice. International journal of cardiology 27 25227892
2013 The CPVT-associated RyR2 mutation G230C enhances store overload-induced Ca2+ release and destabilizes the N-terminal domains. The Biochemical journal 27 23746327
2024 Fibroblast Growth Factor Receptor 4 Promotes Triple-Negative Breast Cancer Progression via Regulating Fatty Acid Metabolism Through the AKT/RYR2 Signaling. Cancer medicine 26 39658878
2022 Increased RyR2 open probability induces neuronal hyperactivity and memory loss with or without Alzheimer's disease-causing gene mutations. Alzheimer's & dementia : the journal of the Alzheimer's Association 26 34985200
2023 Ryanodine receptor 2 (RYR2) dysfunction activates the unfolded protein response and perturbs cardiomyocyte maturation. Cardiovascular research 25 35576474
2021 RYR2 Mutations Are Associated With Benign Epilepsy of Childhood With Centrotemporal Spikes With or Without Arrhythmia. Frontiers in neuroscience 24 33897349
2021 "Ryanopathies" and RyR2 dysfunctions: can we further decipher them using in vitro human disease models? Cell death & disease 24 34725342
2019 Calmodulin inhibition of human RyR2 channels requires phosphorylation of RyR2-S2808 or RyR2-S2814. Journal of molecular and cellular cardiology 24 30928430
2012 Postmortem genetic testing of the ryanodine receptor 2 (RYR2) gene in a cohort of sudden unexplained death cases. International journal of legal medicine 24 22222782
2020 Calcium signaling consequences of RyR2 mutations associated with CPVT1 introduced via CRISPR/Cas9 gene editing in human-induced pluripotent stem cell-derived cardiomyocytes: Comparison of RyR2-R420Q, F2483I, and Q4201R. Heart rhythm 23 32931925
2018 Dynamic and Irregular Distribution of RyR2 Clusters in the Periphery of Live Ventricular Myocytes. Biophysical journal 23 29401432
2019 Diminished inhibition and facilitated activation of RyR2-mediated Ca2+ release is a common defect of arrhythmogenic calmodulin mutations. The FEBS journal 22 31230402
2023 RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease. Journal of molecular and cellular cardiology 21 37285929
2022 Oxidative stress activates Ryr2-Ca2+ and apoptosis to promote PM2.5-induced heart injury of hyperlipidemia mice. Ecotoxicology and environmental safety 21 35091300
2021 Limiting RyR2 open time prevents Alzheimer's disease-related deficits in the 3xTG-AD mouse model. Journal of neuroscience research 21 34352124
2015 R4496C RyR2 mutation impairs atrial and ventricular contractility. The Journal of general physiology 21 26666913
2009 Sudden infant death syndrome in mice with an inherited mutation in RyR2. Circulation. Arrhythmia and electrophysiology 21 20009080
2024 CD38-RyR2 axis-mediated signaling impedes CD8+ T cell response to anti-PD1 therapy in cancer. Proceedings of the National Academy of Sciences of the United States of America 20 38451948
2024 Inhibitors of Intracellular RyR2 Calcium Release Channels as Therapeutic Agents in Arrhythmogenic Heart Diseases. Annual review of pharmacology and toxicology 20 39374431
2017 Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Heart (British Cardiac Society) 20 28237968
2014 Differences in the regulation of RyR2 from human, sheep, and rat by Ca²⁺ and Mg²⁺ in the cytoplasm and in the lumen of the sarcoplasmic reticulum. The Journal of general physiology 20 25156119
2004 Dispersion of ventricular mRNA of RyR2 and SERCA2 associated with arrhythmogenesis in rats. Acta pharmacologica Sinica 20 15169625
2022 How does flecainide impact RyR2 channel function? The Journal of general physiology 18 35713932
2019 Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 18 30615235
2009 Ryanodine receptor (RyR2) mutations in sudden cardiac death: studies in extended pedigrees and phenotypic characterization in vitro. International journal of cardiology 18 19781797
2022 Hippocampal dendritic spines express the RyR3 but not the RyR2 ryanodine receptor isoform. Biochemical and biophysical research communications 17 36344175
2015 Spinal RyR2 pathway regulated by the RNA-binding protein HuD induces pain hypersensitivity in antiretroviral neuropathy. Experimental neurology 17 25765490
2005 The cardiac ryanodine receptor (RyR2) and its role in heart disease. Cardiology in review 17 15831148
2022 Cytosolic Ca2+-dependent Ca2+ release activity primarily determines the ER Ca2+ level in cells expressing the CPVT-linked mutant RYR2. The Journal of general physiology 16 35446340
2019 Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse. Journal of cell science 16 31028179
2023 Increased Ca2+ Transient Underlies RyR2-Related Left Ventricular Noncompaction. Circulation research 15 37325910
2022 LINC01194 recruits NUMA1 to promote ubiquitination of RYR2 to enhance malignant progression in triple-negative breast cancer. Cancer letters 15 35750275
2020 Impact of NR5A2 and RYR2 3'UTR polymorphisms on the risk of breast cancer in a Chinese Han population. Breast cancer research and treatment 15 32572717
2014 Non-ventricular, Clinical, and Functional Features of the RyR2(R420Q) Mutation Causing Catecholaminergic Polymorphic Ventricular Tachycardia. Revista espanola de cardiologia (English ed.) 15 25440180
2013 Malondialdehyde and 4-hydroxynonenal adducts are not formed on cardiac ryanodine receptor (RyR2) and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) in diabetes. Molecular and cellular biochemistry 15 23354458
2021 Novel RyR2 Mutation (G3118R) Is Associated With Autosomal Recessive Ventricular Fibrillation and Sudden Death: Clinical, Functional, and Computational Analysis. Journal of the American Heart Association 14 33686871
2020 Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias. International journal of molecular sciences 14 32260593
2014 RyR2 modulates a Ca2+-activated K+ current in mouse cardiac myocytes. PloS one 14 24747296
2011 Upregulation of RyR2 in hypoxic/reperfusion injury. Journal of neurotrauma 14 21612318
2022 RyR2/IRBIT regulates insulin gene transcript, insulin content, and secretion in the insulinoma cell line INS-1. Scientific reports 13 35562179
2022 RyR2 Serine-2030 PKA Site Governs Ca2+ Release Termination and Ca2+ Alternans. Circulation research 13 36583384
2021 CaMKII inhibition has dual effects on spontaneous Ca2+ release and Ca2+ alternans in ventricular cardiomyocytes from mice with a gain-of-function RyR2 mutation. American journal of physiology. Heart and circulatory physiology 13 34270372
2017 Impact of RyR2 potentiation on myocardial function. American journal of physiology. Heart and circulatory physiology 13 28389603

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