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.[8]
Function
The RYR2 protein functions as the major component of a calcium channel located in the
sarcoplasmic reticulum that supplies ions to the
cardiac muscle 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
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
troponin, which shifts
tropomyosin and allows the
myosinATPase to bind to
actin, enabling cardiac muscle contraction.[9] RYR2 channels are associated with many cellular functions, including mitochondrial metabolism, gene expression and cell survival, in addition to their role in cardiomyocyte contraction.[10]
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."[11]
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.[13] 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.[14]
Interactions
Ryanodine receptor 2 has been shown to
interact with:
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