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

Jue Li1, Pietro Mesirca2, Alicia D’Souza1, Yanwen Wang1, Shu Nakao1, Charlotte Cox1, Jules Hancox3, Matteo Mangoni2, Mark Boyett1
1University of Manchester, 2Université de Montpellier, 3University of Bristol


Abstract

First- and second-degree heart block, resulting from slower conduction of the action potential through the atrioventricular node (AVN), is common in athletes and has been correlated to the intensity and length of training. In swim-trained mice, we previously observed AVN dysfunction characterised by first-degree heart block and a prolonged Wenckebach cycle length. This was concomitant with diffuse transcriptional, protein and functional remodelling of the HCN and L-type Ca2+ channels known to be involved in AVN impulse generation and conduction. Notably, patch clamp recordings in isolated AVN myocytes from swim-trained mice demonstrated a significant reduction of If (by ~60%) and ICa,L (by ~40%) vs. sedentary control mice. The effect of the observed changes in ionic currents were investigated using a one-dimensional computational model of the AVN made up of 100 atrioventricular node elements, each 100 microM in length. This was used in conjunction with a biophysically-detailed model of the AV node action potential from Inada et al.(2009). With the rabbit AVN action potential, on decreasing of If by ~60% and ICa,L by ~40% to mimic the effect of athletic training, the conduction velocity of the AVN was reduced 25% from 0.09462 to 0.07056 m/s. We conclude that ionic remodelling of the AVN is a key mechanism underlying heart block in the athlete.