Ryanodine receptor 2 Antibodies

Ryanodine receptor 2 (RYR2)

Calcium channel that mediates the release of Ca(2+) in the sarcoplasmic reticulum to the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia.

In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels because of stimulation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by creation of heterotetramers with RYR3.

Gene Information

Human
Gene Name:	RYR2
Uniprot:	Q92736
Entrez:	6262

Family

Belongs to:
ryanodine receptor (TC 1.A.3.1) family

Alternative Names

ARVC2arrhythmogenic right ventricular dysplasia 2; ARVD2; Cardiac muscle-type ryanodine receptor; hRYR-2; ryanodine receptor 2 (cardiac); ryanodine receptor 2; RyR2; RYR-2; VTSIPCardiac muscle ryanodine receptor-calcium release channel

Molecular Weight

Mass (kDA):
564.567 kDA

Genomic Context

Human
Location:	1q43
Sequence:	1; NC_000001.11 (237042184..237833988)

Tissue Specificity

Detected in heart muscle (at protein level). Heart muscle, brain (cerebellum and hippocampus) and placenta.

Subcellular Localizations

Sarcoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein. Sarcoplasmic reticulum. The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic.

Diseases

• Tachycardia, Ventricular
• Cardiac Arrhythmia
• Polymorphic Ventricular Tachycardia
• Ventricular Tachycardia, Catecholaminergic Polymorphic, 1 (disorder)
• Sudden Cardiac Death
• Sudden Death
• Cardiomyopathies
• Syncope
• Cardiac Death
• Heart Diseases
• Malignant Paraganglionic Neoplasm
• Arrhythmogenic Right Ventricular Dysplasia
• Long Qt Syndrome

• Heart Failure
• Malignant Hyperpyrexia Due To Anesthesia
• Channelopathies
• Cardiac Fibrillation
• Nervousness
• Bradycardia
• Atrial Fibrillation

Interacting Proteins

• FKBP1A
• FKBP1B
• MDM2

Pathways

• Transport
• Cell Death
• Aging
• Localization
• Pathogenesis
• Hibernation
• Hyperphosphorylation
• Programmed Cell Death
• Electron Transport
• Electron Transport Chain
• Immune Response
• Proteolysis
• Muscle Contraction

• Oxidative Phosphorylation
• Response To Caffeine
• Cardiac Conduction
• Inflammatory Response
• Embryo Development
• Swimming
• Reverse Transcription

PTMs

• Phosphorylation

• Cleavage

• Dephosphorylation

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/RYR2

Best Uses Of The RYR2 Marker In Boster Bio

The RYR2 marker can be used in many applications, including boster disease. There is an imbalance between NO/redox in heart failure. In this state RyR2 can become leaky, leading to elevated Ca2+ levels during diastole and impaired heart contractility. You can read the rest to learn more about RYR2 markers!

XO inhibitors

Researchers have discovered a new category of gene therapy candidates known as RYR2 inhibitors. These compounds block CaMKII (a key enzyme responsible for triggering heart rhythm problems). They were created from induced pluripotent stem cells, which mimics disease's cellular environment. In a new step, they are using these treatments to stimulate the growth of new blood vessels.

Dantrolene was the lead compound that inhibited RyR2 by decreasing RyR2's p o value and increasing RyR2's open and close times. The dantrolene-induced changes to RyR2's P o were similar in 0.1 and 100 mM cytoplasmic Ca 21, but the effect was less at higher concentrations. The dantrolene induced changes in the open time and closed time were not reversible.

Phosphorylation of RYR2 evokes the release of Ca(2+) in the presence of luminal Ca(2+. This Ca(2+) release stimulates the proteasome and promotes PSMC5/RPT6 activate. Phosphorylation also promotes binding of NFKB1 p50-50DNA-binding site. RYR2 inhibition promotes Hh Signaling by preventing the resumption meiosis within prophase-arrested oocytes.

These antibodies have been tested in SP rats. They reversed the increased time to peak and dispersion of Ca2+, while restoring normal atrial Ca2+ handling. They also restored dysfunctional SR Ca2+ releases and decreased the frequency induced CaT alternans. These antibodies are extremely effective in the treatment and prevention of AF. Read on to learn more about the Role RYR2 inhibits in ventricular function.

There are NO donors

The RYR2 gene, which is expressed in the heart, affects the ventricles and atria. While a large number of donors for the marker are healthy, only a few suffer from sudden death. A large number of people have a gene disorder that results in a lower level of mRNA/protein. This type of mutation is linked to atrial fibrillation, and is the cause for CPVT1. It can also be associated with bradycardia, which may cause left ventricular noncompaction and dilated cardiomyopathy.

People with the RYR2 mark have a significantly lower threshold to activate the RYR2 channel. This variant can cause exercise-induced syncope, progressive ventricular dysfunction, and rare bidirectional ventricular arrhythmia. The RYR2 markers can cause a variety a cardiac disorders, since CPVT can be inherited.

Unlike NO donors, the RYR2 gene is highly conserved. Hence, it is essential to understand how the gene's expression is affected by the presence of NO donors. A study found that NO donors to the RYR2 gene had a significantly lower rate for cytokine-induced cytokine generation than control iPSC CMs. Moreover, these cells did not show any differences in the amplitude of their DADs.

Using a TaqMan commercial assay to test for the RYR2 genome, iPSCs derived form patients with the RYR2 chromosome duplication were found having the RYR2 DNA. Clones containing RYR2 were positive in iPSCs, iPSC CMs, and iPSCs. The results of this clone were indistinguishable to unrelated control lines. However, they confirmed that the cells contain the RYR2 genes.

It was interesting to note that there were two large multigenerational Amish families that had the RYR2 mutogenic substrate. This type of mutation affects a small subset of Amish people and has an autosomal-recessive inheritance. These two pedigrees include 23 affected individuals. None of them died unexpectedly. The affected individuals were able to perform normal exercise stress tests and a Holter monitor for 24 hours.

iPSC CMs that express RYR2 markers have action potentials that are very similar to those of WT-control iPSCs. Similar results were observed in iPSCs when the RYR2 markers was present. They also displayed an erratic beating frequency. This is because genetically modified cells are naturally unpredictable. The resulting iPSC CMs have an iPSC marker for the RYR2 gene.

Inhibitors

Antrolene inhibits RyR-channel opening and closing at different concentrations. Antrolene inhibited RyR channels opening and closing by 52% in the presence CaM. This inhibition was also observed in R2474S knockin mice. Hence, dantrolene is a potent inhibitor of RYR-channel activation. Its potency has been tested by inhibiting dantrolene in a concentration 10 nM.

Dantrolene inhibits both RyR areoforms. The drug reduced the P.o of RyR by binding to 100 nM cytoplasmic C21 (12 mMATP). The inhibition was easily reversed by washing. Moreover, this compound inhibits a wide range of cytosolic Ca21 concentrations, from 0.1 mM to 100 mM.

Dantrolene stops RyR2 activity from binding to a target chemical. In a failure heart, it normalises the diastolic Ca2+ leak while inhibiting Ca2+ release during systole. It is toxic and hepatotoxic, so it has limited therapeutic applications. Dantrolene inhibits RyR2's activity in a mouse model suffering from failing hearts. The drug prevents the channels binding to a calcium-ion ion.

Dual-color STED microscopy confirmed that there were junctophilin-2 clusters near caveolin-3-labeled ATSR junctions. However, the inverse overlap in junctophilin-2- and RyR2 was unaffected. Moreover, the inhibitors decreased junctophilin-2-mediated phosphorylation in VMs. This suggests that junctophilin-2 inhibits RYR2 activity.

The results indicate that cardiac junctophilin-2 knockdown increases Ca2+ leaching. However, junctional RyR2 cluster disruption might also affect atrial Ca2+ leaching. Transverse line scanning using cholesterol-PEG-KK114 1 mM (Ca2+) and membrane labeling allowed researchers to visualize Ca2+ transients as sparks in the AM. The results were similar across different hearts, suggesting that there was a correlation.