ROLE OF GAP JUNCTION RESISTANCE IN RATE-INDUCED DELAY IN CONDUCTION IN A CABLE MODEL OF THE ATRIOVENTRICULAR NODE

Abstract

A constant fast heart rate results in a time and rate dependent increase in AV nodal conduction time. The origin of this delay in conduction remains unknown due to limited access to corresponding cellular events. We have investigated the possible contribution of gap junction resistance in rate-induced delay in conduction using a one-dimensional model of the AV node. We use a cable that includes 100 cells: 30 AN cells, 40 N cells and 30 NH cells. The three cell types are modeled by varying the parameters of a modified Beeler Reuter ionic model. N cells have a low density of sodium current and are mainly activated by an ICa,L type current. Their resting potential is less negative and their upstroke slower than those of AN and NH cells. Cells are connected by gap junctions whose resistance is controlled by the intracellular calcium concentration. Stimuli are applied to the first AN cells. At a pacing rate of 400 ms, the gap junction resistance was AN 1.8 MΩ, N 32.0 MΩ and NH 3.6 MΩ and the total conduction time was 48 ms. Following a sudden decrease of cycle length from 400 ms to 250 ms, the conduction time progressively increased and reached a new steady-state of 77.7 ms after 800 beats. This increase of conduction time was mainly caused by a gradual increase of the gap junction resistance between N cells, which reached 46 MΩ at steady state. Rate and time dependent increase of conduction time was abolished when the gap junction resistances were kept constant. This model study suggests that the dynamic changes in gap junction resistance may play a key role in rate-induced AV nodal conduction delay.