Reactive oxygen species and excitation-contraction coupling in the context of cardiac pathology

Abstract

Reactive oxygen species (ROS) are highly reactive oxygen-derived chemical compounds that are by-products of aerobic cellular metabolism as well as crucial second messengers in numerous signaling pathways. In excitation-contraction-coupling (ECC), which links electrical signaling and coordinated cardiac contraction, ROS have a severe impact on several key ion handling proteins such as ion channels and transporters, but also on regulating proteins such as protein kinases (e.g. CaMKII, PKA or PKC), thereby pivotally influencing the delicate balance of this finely tuned system. While essential as second messengers, ROS may be deleterious when excessively produced due to a disturbed balance in Na(+) and Ca(2+) handling, resulting in Na(+) and Ca(2+) overload, SR Ca(2+) loss and contractile dysfunction. This may, in the end, result in systolic and diastolic dysfunction and arrhythmias. This review aims to provide an overview of the single targets of ROS in ECC and to outline the role of ROS in major cardiac pathologies, such as heart failure and arrhythmogenesis. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System"