From mitochondrial ion channels to arrhythmias in the heart: computational techniques to bridge the spatio-temporal scales.
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.
Plank
Gernot
G
Institute of Biophysics, Medical University Graz, 8010 Graz, Austria.
Zhou
Lufang
L
Greenstein
Joseph L
JL
Cortassa
Sonia
S
Winslow
Raimond L
RL
O'Rourke
Brian
B
Trayanova
Natalia A
NA
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
D007473:Ion Channels