Andrew P. Landstrom, Dobromir Dobrev and Xander H.T. Wehrens

Abstract

There has been a significant progress in our understanding of the molecular mechanisms by which
calcium (Ca 2+ ) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene defects can
cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular
tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of
multiple Ca 2+ -handling proteins can contribute to the pathogenesis of arrhythmias in patients with various types
of heart disease. In this review article, we will first review the key role of Ca 2+ in normal cardiac function—in
particular, excitation–contraction coupling and normal electric rhythms. The functional involvement of Ca 2+ in
distinct arrhythmia mechanisms will be discussed, followed by various inherited arrhythmia syndromes caused
by mutations in Ca 2+ -handling proteins. Finally, we will discuss how changes in the expression of regulation of
Ca 2+ channels and transporters can cause acquired arrhythmias, and how these mechanisms might be targeted for
therapeutic purposes. (Circ Res. 2017;120:1969-1993. DOI: 10.1161/CIRCRESAHA.117.310083.)