Phase resetting and dynamics in isolated atrioventricular nodal cell clusters

In the heart, the AV node is the primary conduction pathway between the atria and ventricles and subserves an important function by virtue of its rate-dependent properties. Cell clusters isolated from the rabbit atrioventricular (AV) node beat with a stable rhythm (cycle length: 300-520 ms) and are characterized by slow action potential upstroke velocities (7 to 30 V/s). The goal of this study is to better characterize the phase resetting and the rhythms during periodic stimulation of this slow inward current system. Single or periodic depolarizing pulses (20 ms in duration) were injected into AV nodal cell clusters using glass microelectrodes. Phase resetting curves of both strong, weak as well as discontinuous types were obtained by applying single current pulses of different intensities and latencies following every ten action potentials. Graded responses were elicited in a wide range of stimulus phases and amplitudes. A single premature stimulus caused a transient prolongation of the cycle length. Sustained periodic stimulation, at rates faster than the intrinsic beat rate, resulted in various N:M (stimulus frequency: action potential frequency) entrainment rhythms as well as periodic or irregular changes in action potential morphology. The changes in action potential characteristics were evaluated by computing the area under the action potential trace and above a fixed threshold (-45 mV). We show that the variations in action potential morphology play a major role in the onset of complicated dynamics observed in this experimental preparation. In this context, the prediction of entrainment rhythms using techniques based on the iteration of phase resetting curves (PRCs) is inadequate since the PRC does not carry information directly related to the changes in action potential morphology. This study demonstrates the need to consider graded events which, though not propagated, have important implications in the understanding of dynamical diseases of the heart. (c) 1995 American Institute of Physics.