OVERDRIVE SUPPRESSION OF SPONTANEOUSLY BEATING CHICK HEART CELL AGGREGATES - EXPERIMENT AND THEORY

In spontaneously beating chick heart cell aggregates, sustained period ic stimulation at a rate faster than the intrinsic frequency is genera lly followed by a transient slowing of the automatic rhythm called ''o verdrive suppression.'' We characterize the qualitative aspects of ove rdrive suppression using three sets of experimental protocols: 1) stim ulation at a fixed frequency with various numbers of stimuli, 2) stimu lation at different frequencies, 3) stimulation with different intensi ties. We develop a mathematical model based on a system of nonlinear o rdinary differential equations to account for the experimental observa tions. The main idea of the model is that overdrive suppression arises as a result of a hyperpolarizing current that is induced by action po tentials. This work shows that the frequency of action potentials is t he major determinant of overdrive suppression. Consequently, during pe riodic pacing of spontaneous oscillators at different rates, the faste st frequency where 1:1 entrainment can be maintained is associated wit h maximal overdrive suppression. This type of model is complementary t o the development of a rigorous ionic model and can help provide insig ht into the physiological mechanisms of overdrive suppression.