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(Circulation. 2005;112:2517-2529.)
© 2005 American Heart Association, Inc.

Basic Science for Clinicians

Molecular Basis of Arrhythmias

Manish Shah, MD; Fadi G. Akar, PhD; Gordon F. Tomaselli, MD

From the Department of Medicine, Johns Hopkins University, Baltimore, Md.

Correspondence to Gordon F. Tomaselli, MD, Department of Medicine, Johns Hopkins University, Division of Cardiology, 844 Ross Bldg, 720 Rutland Ave, Baltimore, MD 21205-2196. E-mail gtomasel{at}jhmi.edu

The characterization of single gene disorders has provided important insights into the molecular pathogenesis of cardiac arrhythmias. Primary electricalal diseases including long-QT syndrome, short-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia have been associated with mutations in a variety of ion channel subunit genes that promote arrhythmogenesis. Pathological remodeling of ionic currents and network properties of the heart critical for normal electrical propagation plays a critical role in the initiation and maintenance of acquired arrhythmias. This review focuses on the molecular and cellular basis of electrical activity in the heart under normal and pathophysiological conditions to provide insights into the fundamental mechanisms of inherited and acquired cardiac arrhythmias. Improved understanding of the basic biology of cardiac arrhythmias holds the promise of identifying new molecular targets for the treatment of cardiac arrhythmias.

Key Words: arrhythmia • electrophysiology • genetics • ion channels • molecular biology

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