Overdrive suppression of spontaneously beating chick heart cell aggregates: experiment and theory

In spontaneously beating chick heart cell aggregates, sustained periodic stimulation at a rate faster than the intrinsic frequency is generally followed by a transient slowing of the automatic rhythm called "overdrive suppression." We characterize the qualitative aspects of overdrive suppression using three sets of experimental protocols: 1) stimulation at a fixed frequency with various numbers of stimuli, 2) stimulation at different frequencies, 3) stimulation with different intensities. We develop a mathematical model based on a system of nonlinear ordinary differential equations to account for the experimental observations. The main idea of the model is that overdrive suppression arises as a result of a hyperpolarizing current that is induced by action potentials. This work shows that the frequency of action potentials is the major determinant of overdrive suppression. Consequently, during periodic pacing of spontaneous oscillators at different rates, the fastest frequency where 1:1 entrainment can be maintained is associated with maximal overdrive suppression. This type of model is complementary to the development of a rigorous ionic model and can help provide insight into the physiological mechanisms of overdrive suppression.