Under normal physiologic conditions, the dominant pacemaker cells of the heart lie within the sinoatrial node; in adults, these pacemaker cells fire at rates between 60 to 100 beats per minute (i.e., faster than cells in any other cardiac region, See Figure 3). Even at rest, modulation by the autonomic nervous system dominates, with the primary drive from the parasympathetics; at rest or during sleep, the sinoatrial nodal rate decreases to about 75 beats per minute (bpm) or even slower.

In addition to pacemaker cells of the sinoatrial node, other cells within the conduction system are capable of developing autorhythmicity, specifically those within the atrioventricular node (junction region) and His-Purkinje system. Yet, rhythms generated within these cells are in a much lower range (25 to 55 bpm), hence not altering the intrinsic atrial rates (Figure 2). These lower rate rhythms are commonly referred to as ventricular escape rhythms and are important for patient survival, since they maintain some degree of cardiac output in situations when the sinoatrial and/or atrioventricular nodes are functioning inappropriately (e.g., in a patient with atrial fibrillation). Note that the various populations of pacemaker myocytes (i.e., in the sinoatrial and atrioventricular nodes) elicit so-called slow type action potentials (slow response action potential; see below).