Ryanodine receptor 2

Ryanodine receptor 2 (RYR2) is a is_associated_with::protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 is_associated_with::gene. In the process of cardiac is_associated_with::calcium-induced calcium release, 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 is_associated_with::sarcoplasmic reticulum that supplies ions to the cardiac muscle during is_associated_with::systole. To enable cardiac muscle contraction, calcium influx through voltage-gated is_associated_with::L-type calcium channels in the plasma membrane allows calcium ions to bind to RYR2 located on the is_associated_with::sarcoplasmic reticulum. This binding causes the release of calcium through RYR2 from the sarcoplasmic reticulum into the cytosol, where it binds to the C domain of is_associated_with::troponin, which shifts is_associated_with::tropomyosin and allows the is_associated_with::myosin is_associated_with::ATPase to bind to is_associated_with::actin, 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 is_associated_with::catecholaminergic polymorphic ventricular tachycardia, is_associated_with::stress-induced polymorphic ventricular tachycardia, and is_associated_with::arrhythmogenic right ventricular dysplasia.

Mice with genetically reduced RYR2 exhibit a lower basal heart rate and fatal arrythmias.

Interactions
Ryanodine receptor 2 has been shown to interact with:


 * is_associated_with::AKAP6,
 * is_associated_with::PRKACA,
 * is_associated_with::PRKACB,
 * is_associated_with::PRKACG, and
 * SRI.