Reducing complexity and unidentifiability when modelling human atrial cells

Mathematical models of a cellular action potential in cardiac modelling have become increasingly complex, particularly in gating kinetics which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalised medicine to inform clinical decision- making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty from the parameter posterior distributions. Two approaches are investigated to reduce the uncertainty present: firstly to re-calibrate the models to a more complete ‘unified’ dataset and, secondly, the use of a standardised formulation with fewer parameters to constrain. The study shows that the use of more complete datasets does not eliminate uncertaint...