New Mathematical Model of Electromechanical Coupling in Rat Cardiomyocytes

Leonid Katsnelson, Pavel Konovalov, Olga Solovyova
Institute of Immunology and Physiology of the RAS at Ekaterinburg


Abstract

Only one mathematical model of the excitation-contraction coupling (ECC) in the rat cardiomyocytes, the Pandit–Hinch–Niederer model (PHN) seems published so far (see e.g. Niederer and Smith; BJ, 2007). Simulation of the slow force response after the myocardium stretch was significant achievement of the PHN. For this the authors had to introduce additionally stretch-activated channels in the Pandit-model of the Action Potential (AP) used as electrophysiological module of the PHN, while such channels were not accounted for in the original Pandit-model (Pandit ea; BJ, 2001). Significant limitation of the PHN is incapacity to simulate quick effects of the length changes, i.e. Mechano-Calcium and Mechano-Electric Feedback effects (MCMEF) manifesting themselves during the twitches of cardiac muscles (trabeculae, papillary muscles) in a number of important phenomena, including the load-dependence of relaxation. We present here a new model of ECC in the rat cardiomyocyte where we combine the Pandit-model and Hinch-model of calcium handling (Hinch ea; BJ, 2004) with the module of the mechanical activity early developed for the 'Ekaterinburg-Oxford' mathematical model (EO-model) (Sulman ea; BMB, 2008). EO-model describes ECC in intact cardiomyocytes for some species of laboratory animals (e. g. rabbit, guinea pig), being parametrically adapted to each particular one. However, EO-model cannot be applied to simulate adequately the rat AP due to the very specific features of the latter. Inclusion of the Pandit-model of the rat AP is a way to overcome this drawback. Mechanisms of cooperativity of regulatory and contractile proteins is a key link of our module of the mechanical activity that earlier allowed us to simulate within the EO-model a wide range of the MCMEF effects in myocardium. In our new model of the rat cardiomyocytes these effects (including the load-dependence of relaxation) also turn out to be reproduced and result from the cooperativity mechanisms.