Origin and function of the cardiac pacemaker

Abstract

The rhythmic beating of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination is crucial for survival. Abnormalities account for a number of congenital and acquired heart defects in humans. In the mammalian heart, the dominant pacemaker is situated in the sinoatrial node in the upper wall of the right atrium. Specialised myocardial cells develop the potential to generate spontaneous electrical activity. Discrete conduction pathways transmit the electrical signal to the working cardiomyocytes, stimulating muscle contractions. A network of transcription factors controls patterning of the sinoatrial node and surrounding working myocardium. The underlying mechanisms of pacemaker cell development and function are still not fully understood. The heart shows high evolutionary conservation. Intrinsic pacemaker systems are already present in invertebrates and are believed to have evolved in an ancestral bilaterian. On the molecular level, pacemaker mechanisms are less well understood in lower vertebrates. The zebrafish Danio rerio has emerged as a promising model to study pacemaker development and function. Detailed characterisation of its pacemaker system is required to tap the full potential of the extensive experimental techniques available in zebrafish.