Sulfur Dioxide Effects on Human Atrial Action Potential. In Silico Study

Catalina Tobon1, Juan P Ugarte2, Laura C Palacio3, Javier Saiz4
1Universidad de Medellin, 2Universidad de San Buenaventura, 3MATBIOM, Universidad de Medellin, 4Ci2B, Universitat Politècnica de València


Abstract

Background: Human exposure to air pollutants agents, like sulfur dioxide (SO2), has significant effects on the cardiovascular system. Studies have shown that SO2 blocks the L-type calcium channel and increases the sodium channel (INa), the transient outward potassium current (Ito) and the inward rectifying potassium current (IK1), which implies an action potential duration (APD) decrease, increasing the risk of initiation and maintenance of cardiovascular disease such as atrial arrhythmias. Aim: This study aims to assess the effects of the SO2 at different concentrations on human atrial action potential, using computational simulation. Methods: Based on experimental data, we developed concentration-dependent equations to simulate the SO2 effects on ICaL, INa, Ito and IK1. They were incorporated in the Courtemanche model of human atrial cell in a unicellular environment and in a 2D model of atrial tissue. Pacing was applied at a basic cycle length of 1000 ms. The APD at 90% of the repolarization (APD90) and the resting membrane potential (RMP) were measured. S1-S2 cross-field protocol was applied to initiate a rotor. SO2 concentrations from 0 to 1000 µM were implemented. Results: Our results in a human atrial cell model are in agreement with results from non-human in vitro and in vivo studies. The SO2 causes the APD shortening and loss of plateau phase of the action potential in a fraction that increases as the concentration increases. For the highest SO2 concentration (1000 µM), the ICaL peak decreases by 95%, the INa, Ito and IK1 peaks increases by 77%, 147% and 96%, respectively, and the APD90 decreases by 81%. The RMP does not show significant changes. In the 2D model, a rotor can be generated from 100 µM of SO2 concentration. Conclusion: Our results show pro-arrhythmic effects of SO2 expressed through APD shortening and a rotor generation, during normal electrophysiological conditions.