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Ca2+ Release Channels (Ryanodine Receptors) and Arrhythmogenesis

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Electrical Diseases of the Heart

Abstract

Intracellular calcium (Ca2+) release channels (ryanodine receptors type 2, RyR2) are present on the sarcoplasmic reticulum (SR) in cardiomyocytes and are required for excitation-contraction coupling in cardiac muscle. RyR2s are macromolecular channel complexes associated with regulatory proteins that modulate RyR2 function in response to extracellular signals. Recent studies have provided new mechanistic insight into the role of diastolic SR Ca2+ leak through RyR2 as a trigger for a wide range of cardiac arrhythmias. RyR2 has been implicated to play a central role in arrhythmias associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), heart failure (HF) and drug-induced arrhythmias. At present, there is no FDA approved medication that selectively targets RyR2. However, novel therapeutic approaches are being evaluated to correct defective RyR2 Ca2+ release based on recent advances in the understanding of the cellular mechanisms underlying arrhythmias in HF and CPVT.

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Acknowledgment.

X.H.T.W. is a W.M. Keck Foundation Distinguished Young Scholar in Medical Research, and is supported by NIH/NHLBI grants R01-HL089598 and R01-HL091947, and Muscular Dystrophy Association grant #69,238. S.A. is supported by American Heart Association SCA predoctoral fellowship (2010–2012) and fellowship from Alkek foundation.

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  1. Division of Cardiology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Room 506C, Mail Stop 335, Houston, TX, 77030, USA

    Sameer Ather MD, PhD

  2. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM335, Houston, TX, 77030, USA

    Xander H. T. Wehrens MD, PhD

  3. Division of Cardiology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, BCM335, Houston, TX, 77030, USA

    Xander H. T. Wehrens MD, PhD

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  1. Sameer Ather MD, PhD
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Correspondence to Xander H. T. Wehrens MD, PhD .

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  1. , Department of Internal Medicine, UMDNJ-RWJ Medical School, Robert Wood Johnson Pl. 1, New Brunswick, 08903-0019, New Jersey, USA

    Ihor Gussak

  2. , Gordon K. Moe Scholar, Masonic Medical Research Laboratory, Bleecker Street, Utica, 13501-1787, New York, USA

    Charles Antzelevitch

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Ather, S., Wehrens, X.H.T. (2013). Ca2+ Release Channels (Ryanodine Receptors) and Arrhythmogenesis. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4881-4_17

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