Detecting undetectables: Can conductances of action potential models be changed without appreciable change in the transmembrane potential?

Chaos
Karoline Horgmo JægerAslak Tveito

Abstract

Mathematical models describing the dynamics of the cardiac action potential are of great value for understanding how changes to the system can disrupt the normal electrical activity of cells and tissue in the heart. However, to represent specific data, these models must be parameterized, and adjustment of the maximum conductances of the individual contributing ionic currents is a commonly used method. Here, we present a method for investigating the uniqueness of such resulting parameterizations. Our key question is: Can the maximum conductances of a model be changed without giving any appreciable changes in the action potential? If so, the model parameters are not unique and this poses a major problem in using the models to identify changes in parameters from data, for instance, to evaluate potential drug effects. We propose a method for evaluating this uniqueness, founded on the singular value decomposition of a matrix consisting of the individual ionic currents. Small singular values of this matrix signify lack of parameter uniqueness and we show that the conclusion from linear analysis of the matrix carries over to provide insight into the uniqueness of the parameters in the nonlinear case. Using numerical experiments, we qu...Continue Reading

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Citations

Feb 23, 2020·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Dominic G WhittakerGary R Mirams
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