The sinoatrial node in the heart is composed of pacemaker cells which generate the heartbeat. Individual pacemaker cells exhibit substantial heterogeneity in their electrophysiological properties. Recently, we discovered that sinoatrial node cells can switch abruptly between a firing mode, in which they regularly fire action potentials, and a nonfiring mode, in which they stop firing for a certain period of time. Within the sinoatrial node network, firing and nonfiring cells interact electrically via gap junctions. Nonfiring cells slow action potential frequency in cells with intrinsic automaticity and, conversely, firing cells recruit nonfiring cells to fire. This mechanism is termed tonic entrainment and is important for the ability of the leading pacemaker region to generate regular electrical discharges that control electrical activation of the entire heart. Most importantly, this mechanism can be tuned by the autonomic nervous system. We show that the proportion of firing cells can be increased by the sympathetic nervous system via cAMP-dependent regulation of the pacemaker ion channel HCN4, thereby stabilizing sinus node function. Lack of cAMP regulation of HCN4 in a genetic mouse model results in inappropriately increased SAN heart rate responses to vagal nerve activity in vivo, sinus bradycardia, dysrhythmia and chronotropic incompetence.