Heart Block in the Athlete - Role of Ion Channel Remodelling as Studied Using a One-dimensional Computational Model of the Atrioventricular Node

Abstract

In swim-trained mice, we previously observed atrioventricular (AV) node dysfunction characterised by first-degree heart block and a prolonged Wenckebach cycle length. Notably, patch clamp recordings from isolated AV node myocytes demonstrated a significant reduction of If (by ~60%) and ICa,L (by ~40%) in swimtrained mice as compared to sedentary control mice. The effect of the observed changes in ionic currents was investigated using a one-dimensional computational model of the AV node. This was used in conjunction with a biophysically-detailed model of the rabbit AV node action potential. On decreasing If by ~60% and ICa,L by ~40% to mimic the effect of athletic training, the conduction velocity of the AV node model was reduced by 25% from 9.5 to 7.1 cm/s. The reduction was solely the result of the decrease in ICa,L. The decrease in If (modelled in the conventional way as a time-dependent hyperpolarization-activated inward current) had no effect on the conduction velocity, despite experimental evidence that If can affect AV node conduction. However, if the model of If was modified to incorporate an instantaneous current, the decrease in If also contributed to the reduction in the conduction velocity. We conclude that ionic remodelling of the AV node is a key mechanism underlying heart block in the athlete.