The coupled-clock pacemaker cell system. The same regulatory factors or nodes (red lettering) couple intracellular Ca2+ to surface-membrane proteins to generate rhythmic spontaneous action potentials at rest. β-adrenergic and cholinergic receptor activation change action potential firing rate via signaling through the same nodes. Musical notes at the ion channels and also same notes during action potential schematically illustrate the sequence of their activation underlying rhythmic and robust pacemaker function.