Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

found primarily in

cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

. In humans, it is encoded by the ''RYR2''

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. In the process of cardiac

calcium-induced calcium release Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca2+ stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for ...

, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.

Structure

The channel is composed of RYR2 homotetramers and FK506-binding proteins found in a 1:4 stoichiometric ratio. Calcium channel function is affected by the specific type of FK506 isomer interacting with the RYR2 protein, due to binding differences and other factors.

Function

The RYR2 protein functions as the major component of a calcium channel located in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are ke ...

that supplies ions to the

during systole. To enable cardiac muscle contraction, calcium influx through voltage-gated L-type calcium channels in the plasma membrane allows calcium ions to bind to RYR2 located on the

. This binding causes the release of calcium through RYR2 from the sarcoplasmic reticulum into the cytosol, where it binds to the C domain of

troponin image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL Troponin, ...

, which shifts tropomyosin and allows the myosin ATPase to bind to

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

, enabling cardiac muscle contraction. RYR2 channels are associated with many cellular functions, including mitochondrial metabolism, gene expression and cell survival, in addition to their role in cardiomyocyte contraction.

Clinical significance

Deleterious mutations of the ryanodine receptor family, and especially the RYR2 receptor, lead to a constellation of pathologies leading to both acute and chronic heart failure collectively known as "Ryanopathies." Mutations in the ''RYR2'' gene are associated with

catecholaminergic polymorphic ventricular tachycardia Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur du ...

and

arrhythmogenic right ventricular dysplasia Arrhythmogenic cardiomyopathy (ACM), arrhythmogenic right ventricular dysplasia (ARVD), or arrhythmogenic right ventricular cardiomyopathy (ARVC), most commonly is an inherited heart disease. ACM is caused by genetic defects of the parts of hea ...

. Recently, sudden cardiac death in several young individuals in the Amish community (four of which were from the same family) was traced to homozygous duplication of a mutant RyR2 gene. Normal (wild type) RyR2 functions primarily in the myocardium (heart muscle). Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrhythmias.

Interactions

Ryanodine receptor 2 has been shown to interact with: * AKAP6, * PRKACA, * PRKACB, * PRKACG, and *

SRI Shri (; , ) is a Sanskrit term denoting resplendence, wealth and prosperity, primarily used as an honorific. The word is widely used in South and Southeast Asian languages such as Marathi, Malay (including Indonesian and Malaysian), Javanes ...

References

External links

GeneReviews/NCBI/NIH/UW entry on Catecholaminergic Polymorphic Ventricular Tachycardia

GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant

OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant
* {{Ion channels, g1 Ion channels EF-hand-containing proteins