Pacemaking in the heart: a redundant and robust system of mutually entrained oscillators driving cardiac automaticity

The heart is an electrically controlled, mechanical pump that provides a constant supply of blood to the body. It is not surprising, then, that the heartbeat, which occurs on average one or twice every second and over 2.5 billion times without fail in most lifetimes, is maintained by a redundant and robust pacemaking system that ensures regular, rhythmic cardiac excitation. This excitation is initiated in the sinoatrial node (the heart's natural pacemaker), which displays intrinsic spontaneous electrical activity, responsible for the heart's automaticity. As part of the special issue on Pacemaking in Multicellular Organ Systems, in this review we provide a basic overview of the mechanisms responsible for cardiac automaticity intended for a general audience - to allow for comparison with other organs in which pacemaking activity is present - and discuss often overlooked factors critical for integrated cardiac pacemaker function. Ultimately, we hope that a better understanding of pacemaking in the heart, and how it relates to that seen in other organs, will improve our overall understanding of physiological cardiac function, automaticity observed in experimental model systems, and aberrant excitation responsible for deadly cardiac arrhythmias.