Multiple Regression Analysis of Parameter Sensitivity in Ventricular Myocyte Model

electrophysiological computational models of cardiac ventricular myocyte are often times complex and involve numerous parameters and component interactions. Therefore, a viable method is required to assess model stability and to learn about the physiological interactions between various parameters. A holistic study of cardiac myocyte may explain important disease pathologies and offer insights into potential treatment options. Since an in silico experiment is easy to manipulate and allows the investigator to collect large-scale data sets, one can use statistical methods to study model outcomes and qualitatively evaluate parameter sensitivity in relation to the outputs. Furthermore, statistical methods can correlate multiple variables and identify novel interactions that are oftentimes elusive in in vitro experiments. Sobie (2009) suggested the use of partial least square regression as an exploratory analysis tool in analysing parameter sensitivity in electrophysiological models. He demonstrated its potential as a viable method for characterizing and assessing computational models. In this report I extend the use of PLS regression – in conjunction with Nimrod/E experimental design – as theory confirmation tools to assess Shannon-Bers ventricular myocyte model and also to examine new features of the model or shortfalls that could compromise its modelling capabilities. NOTATIONS GCaL SL L-type Ca channel conductance GK1 SL inward rectifier K channel conductance Krel SR Ca-induced Ca release channel CICR conductance Kup SR Ca uptake (SERCA) channel (Ca ATPase) conductance Gtoslow SL Transient outward K channel conductance GKr SL rapid delayed rectifier K current conductance GClbk SL background Cl (leak) channel conductance KNaK SL Na-K exchanger current (low sensitivity) conductance KNCX SL Na-Ca exchanger current conductance GNa Na conductance GNab Na background conductance GCaK K permeability of L-type Ca current GCaNa Na permeability of L-type Ca conductance GCab Ca background conductance Gto transient outward K conductance GKs slowed delayed inward rectifier K conductance GCl Ca-activated Cl current conductance Kleak passive SR Ca leak scaling factor KpCa SL Ca pump current conductance