Propagation of parametric uncertainty for the K+ channel model in mouse ventricular myocytes.

Abstract

Cardiac potassium (K+) channel plays an important role in cardiac electrical signaling. Mathematical models have been widely used to investigate the effects of K+ channels on cardiac functions. However, the model of K+ channel involves parametric uncertainties, which can be induced by fitting the model's parameters that best capture experimental data. Since the prediction of cardiac functions are highly parameter-dependent, it is critical to quantify the influence of parametric uncertainty on the model responses to provide the more reliable predictions. This paper presents a new method to efficiently propagate the uncertainty on the model's parameters of K+ channel to the gating variables as well as the current density. In this way, we can estimate the model predictions and their corresponding confidence intervals simultaneously. A generalized polynomial chaos (gPC) expansion approximating the parametric uncertainty is used in combination with the physical models to quantify and propagate the parametric uncertainties onto the modeled predictions of steady state activation and steady state inactivation of the K+ channel. Using Galerkin projection, the variation (i.e., confidence interval) of the gating variables resulting from the uncertainty of model parameters can then be estimated in a computationally efficient fashion. As compared with the Monte Carlo (MC) simulations, the proposed methodology shows it's advantageous in terms of computational efficiency and accuracy, thus demonstrating the potential for dealing with more complicated cardiac models.