Effects of quasi-steady-state reduction on biophysical models with oscillations

• Published in: Journal of theoretical biology Vol. 393; pp. 16 - 31
• Main Authors: Boie, Sebastian, Kirk, Vivien, Sneyd, James, Wechselberger, Martin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 21-03-2016
• Subjects: Animals; Axons - metabolism; Biological oscillators; Biophysical Phenomena; Dimension reduction; Gonadotropin-Releasing Hormone - metabolism; Membrane Potentials; Models, Neurological; Models, Theoretical; Multiple timescales; Quasi-steady-state reduction; Dimension reduction; Multiple timescales; Quasi-steady-state reduction; Biological oscillators
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2015.12.011

Many biophysical models have the property that some variables in the model evolve much faster than others. A common step in the analysis of such systems is to simplify the model by assuming that the fastest variables equilibrate instantaneously, an approach that is known as quasi-steady state reduction (QSSR). QSSR is intuitively satisfying but is not always mathematically justified, with problems known to arise, for instance, in some cases in which the full model has oscillatory solutions; in this case, the simplified version of the model may have significantly different dynamics to the full model.
This paper focusses on the effect of QSSR on models in which oscillatory solutions arise via one or more Hopf bifurcations. We first illustrate the problems that can arise by applying QSSR to a selection of well-known models. We then categorize Hopf bifurcations according to whether they involve fast variables, slow variables or a mixture of both, and show that Hopf bifurcations that involve only slow variables are not affected by QSSR, Hopf bifurcations that involve fast and slow variables (i.e., singular Hopf bifurcations) are generically preserved under QSSR so long as a fast variable is kept in the simplified system, and Hopf bifurcations that primarily involve fast variables may be eliminated by QSSR. Finally, we present some guidelines for the application of QSSR if one wishes to use the method while minimising the risk of inadvertently destroying essential features of the original model.
•Quasi-steady-state reduction can destroy oscillations in biophysical models.•Some mechanisms for the onset of oscillations are robust under QSSR.•Systematic risk mitigation for QSSR in systems with multiple timescales.•QSSR can introduce new bifurcations of equilibria and periodic orbits.