ROS regulation of microdomain Ca2+ signalling at the dyads

Reactive oxygen species (ROS) are emerging as centre-stage players in cardiac functional regulation. ROS and Ca-2 signals converge at dyads, the structural and functional units of cardiac excitationcontraction coupling. These two prominent signalling systems are intertwined with ROS modulation of the entire Ca-2-signalling network, and vice versa. While constitutively generated homoeostatic ROS are important in setting the redox potential of the intracellular milieu, dynamic signalling ROS shape microdomain and global Ca-2 signals on both the beat-to-beat and greater time scales. However, ROS effects are complex and subtle, characterized by multiphasic and bidirectional Ca-2 responses; and sustained oxidative stress may lead to compromised contractility and arrhythmogenicity. These new understandings should be leveraged to harness ROS for their beneficial roles while avoiding deleterious effects in the heart.