Potential pharmacological therapies for atrial fibrillation. A computational study

Ionic mechanisms underlying atrial fibrillation (AF) generation and propagation are unclear. In this study, we investigate the dependence of AF related properties to changes in human atrial ion channel characteristics by systematically conducting a sensitivity analysis. Cell and tissue simulations are performed using the Maleckar action potential computational model for control and AF remodeling conditions, and are validated using experimental data from the literature. Inward rectifier K⁺ current is shown to play a key role in many of the analyzed cell properties: action potential duration (APD), resting membrane potential and APD restitution slopes; as well as in tissue refractory period and wavelength. Na⁺/K⁺ pump is essential in APD adaptation to heart rate changes and important in the tissue refractory period as well. FastNa⁺ current is proven to be of great significance in tissue simulations, especially altering tissue excitability and, consequently, conduction velocity. Ionic mechanisms underlying electrophysiological properties are similar in control and AF. Sensitivity of AF related properties to changes in ion channel characteristics can help in the design and screening of new multi-channel action anti-AF drugs.