title: From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales.
abstract: Computer simulations of electrical behaviour in the whole ventricles have become commonplace during the last few years. The goals of this article are (i) to review the techniques that are currently employed to model cardiac electrical activity in the heart, discussing the strengths and weaknesses of the various approaches, and (ii) to implement a novel modelling approach, based on physiological reasoning, that lifts some of the restrictions imposed by current state-of-the-art ionic models. To illustrate the latter approach, the present study uses a recently developed ionic model of the ventricular myocyte that incorporates an excitation-contraction coupling and mitochondrial energetics model. A paradigm to bridge the vastly disparate spatial and temporal scales, from subcellular processes to the entire organ, and from sub-microseconds to minutes, is presented. Achieving sufficient computational efficiency is the key to success in the quest to develop multiscale realistic models that are expected to lead to better understanding of the mechanisms of arrhythmia induction following failure at the organelle level, and ultimately to the development of novel therapeutic applications.
authors.affiliation: Institute of Biophysics, Medical University Graz, 8010 Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Plank
authors.forename: Lufang
authors.initials: L
authors.lastname: Zhou
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Greenstein
authors.forename: Sonia
authors.initials: S
authors.lastname: Cortassa
authors.forename: Raimond L
authors.initials: RL
authors.lastname: Winslow
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Trayanova
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D003198:Computer Simulation; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels; D008928:Mitochondria; D008955:Models, Cardiovascular
chemical_list: D007473:Ion Channels