ABSTRACT
Spontaneously beating embryonic chick atrial heart cell aggregates were stimulated with depolarizing current pulses delivered at a fixed delay after each action potential. This preparation is an experimental model of a reentrant tachycardia. During fixed-delay stimulation, bursting behavior was typically observed for a wide range of delays. Episodes of bursting at a rate faster (slower) than control were followed by overdrive suppression (underdrive acceleration). We use a simple nonlinear model, based on the interaction between excitability and overdrive suppression, to describe these dynamics. A modified version of the Shrier-Clay ionic model of electrical activity of the embryonic chick heart cell aggregates that includes a simplified Na+ pump term is also presented. We show that the complex patterns during fixed-delay stimulation arise as a result of delicate interactions between overdrive suppression and phase resetting, which can be described in terms of the underlying ionic mechanisms. This study may provide a basis for understanding incessant tachycardias in the intact heart, as well as an alternative mechanism for the emergence of bursting activity in other biologic tissue.
Subject(s)
Heart/physiology , Models, Cardiovascular , Action Potentials , Animals , Cell Aggregation , Cells, Cultured , Chick Embryo , Electric Stimulation , Kinetics , Mathematics , Membrane Potentials , Myocardium/cytology , Sodium-Potassium-Exchanging ATPase/metabolism , Time FactorsABSTRACT
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.
