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Ryanodine receptor dysfunction in human disorders.
Regulation of intracellular calcium (Ca2+ ) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca2+ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca2+ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca2+ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurodegenerative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.
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