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Calcium Release Channels (Ryanodine Receptors) and Arrhythmogenesis

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Electrical Diseases of the Heart

Abstract

Intracellular calcium release channels (ryanodine receptors, RyR) are present on the sarcoplasmic reticulum (SR) in cardiomyocytes and are required for excitation-contraction (EC) coupling in cardiac muscle. Each RyR channel consists of four pore-forming subunits that contain large cytoplasmic domains, which serve as scaffolds for proteins that regulate the activity of the channel. An important regulatory protein is calstabin2 (FKBP12.6), a subunit that stabilizes the closed state of the channel to prevent aberrant calcium (Ca2+) leak from the SR.1 Direct targeting of several protein kinases and phosphatases to the type 2 cardiac RyR channel (RyR2) allows for rapid and localized modulation of SR Ca2+ release in response to extracellular signals.2

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Sood, S., Wehrens, X.H. (2008). Calcium Release Channels (Ryanodine Receptors) and Arrhythmogenesis. In: Gussak, I., Antzelevitch, C., Wilde, A.A.M., Friedman, P.A., Ackerman, M.J., Shen, WK. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-84628-854-8_14

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