Calcium Signaling and Cardiac Arrhythmias

There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca²⁺) 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 Ca²⁺-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 Ca²⁺ in normal cardiac function-in particular, excitation-contraction coupling and normal electric rhythms. The functional involvement of Ca²⁺ in distinct arrhythmia mechanisms will be discussed, followed by various inherited arrhythmia syndromes caused by mutations in Ca²⁺-handling proteins. Finally, we will discuss how changes in the expression of regulation of Ca²⁺ channels and transporters can cause acquired arrhythmias, and how these mechanisms might be targeted for therapeutic purposes.