Ryanodine Receptor-Targeted Anti-Arrhythmic Therapy

Authors

  • XANDER H.T. WEHRENS,

    1. Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
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  • STEPHAN E. LEHNART,

    1. Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
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  • ANDREW R. MARKS

    Corresponding author
    1. Department of Physiology and Cellular Biophysics, Center for Molecular Cardiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    2. Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA
    • Address for correspondence: Prof. Andrew R. Marks, M.D., Department of Physiology and Cellular Biophysics, Columbia University College of Physicians & Surgeons, P&S 1–511, 630 West 168th Street, New York, NY 10032, USA. Voice: 212-305-0272; fax: 212-305–3690. arm42@columbia.edu

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Abstract

Abstract: Cardiac arrhythmia is an important cause of death in patients with heart failure (HF) and inherited arrhythmia syndromes, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). Alterations in intracellular calcium handling play a prominent role in the generation of arrhythmias in the failing heart. Diastolic calcium leak from the sarcoplasmic reticulum (SR) via cardiac ryanodine receptors (RyR2) may initiate delayed afterdepolarizations and triggered activity leading to arrhythmias. Similarly, SR Ca2+ leak through mutant RyR2 channels may cause triggered activity during exercise in patients with CPVT. Novel therapeutic approaches, based on recent advances in the understanding of the cellular mechanisms underlying arrhythmias in HF and CPVT, are currently being evaluated to specifically correct defective Ca2+ release in these lethal syndromes.

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