Changes in heart rate elicited by vagal activity: a model study

The cellular mechanisms responsible for changes in sinus cycle length elicited by vagal stimulation were studied by means of a mathematical model. The model incorporated a stimulation-mediated depletion of the releasable pool of acetylcholine in the nerve endings, degradation of acetylcholine in the neuroeffector junction, and a model of the electrical activity of a pacemaker cell based on the kinetics of six membrane ionic channels. The results obtained explain the underlying mechanisms of experimentally observed phenomena such as the linear increase in sinus cycle length with frequency of vagal stimulation, the shape of the phase response curve, oscillations in sinus cycle length (sinus arrhythmia), and synchronization (entrainment) of the sinus node by constant-frequency vagal stimulation