Restitution of Ca(2+) release and vulnerability to arrhythmias

New information has recently been obtained along two essentially parallel lines of research: investigations into the fundamental mechanisms of Ca(2+)-induced Ca(2+) release (CICR) in heart cells, and analyses of the factors that control the development of unstable rhythms such as repolarization alternans. These lines of research are starting to converge such that we can begin to understand unstable and potentially arrhythmogenic cardiac dynamics in terms of the underlying mechanisms governing not only membrane depolarization and repolarization but also the complex bidirectional interactions between electrical and Ca(2+) signaling in heart cells. In this brief review, we discuss the progress that has recently been made in understanding the factors that control the beat-to-beat regulation of cardiac Ca(2+) release and attempt to place these results within a larger context. In particular, we discuss factors that may contribute to unstable Ca(2+) release and speculate about how instability in CICR may contribute to the development of arrhythmias under pathological conditions.