A Global Sensitivity Index for Biophysically Detailed Cardiac Cell Models: A Computational Approach

Biophysically detailed cardiac cell models are based upon stiff ordinary differential equations describing ionic channels and intracellular dynamics aiming at reproducing experimental action potentials (APs) and intracellular calcium ([

$Ca^{2+}]_{i}$

) transients. Channel blocking and bifurcation analyses are local sensitivity analyses in model parameter space. However, all parameters influence model behaviour and require a global sensitivity index quantifying the influence of parameters on model responses. Identification of the influence of individual parameters increases our understanding of models. A global parameter sensitivity index for assessing the sensitivity of model responses to parameters in cardiac cell models is proposed. The robust index was applied to four widely used models. The analysis revealed that whilst models have common sets of parameters influencing AP and

$[Ca^{2+}]_{i}$

transients, there are subtle differences. This sensitivity analysis offers a systematic method for quantifying the influence of individual parameters on model behaviour to assist in model reduction, refinement or development.