Abstract
Though congestive heart failure is a leading cause of death in our population, the pathophysiological mechanisms at molecular level remain to be elucidated. This paper discusses the contribution of NCX to the pathological pattern of intracellular calcium regulation and contraction on the basis of computer simulations of a virtual cell. The model comprises calcium handling mechanisms, troponin control and acto-myosin interactions. The contribution of NCX was studied by changing its activity and turning it off for some simulations.It was found that NCX helps to support diastolic function by reducing the Ca2 level during the diastole. At the same time there is a reduction in peak Cai and hence contraction. However, increased NCX activity does not seem to improve calcium handling and contraction crucially, as has been suggested by some authors.
Highlights
The number of known molecular of cardiac excitation-contraction coupling (ECC) mechanisms is enormous and is still growing
It has become impossible to intuitively assess the relative contribution of an individual arrangement in physiological and pathophysiological events. Such understanding is essential for identifying strategies for treating various types of heart failure
The aim of the present study is to assess the relative contribution of Na+/Ca2+ exchanger (NCX) and SERCA to the function of cardiac myocytes and to help interpret experimental data
Summary
The number of known molecular of cardiac excitation-contraction coupling (ECC) mechanisms is enormous and is still growing. It has become impossible to intuitively assess the relative contribution of an individual arrangement in physiological and pathophysiological events. Such understanding is essential for identifying strategies for treating various types of heart failure. Mathematical modeling and simulation offers a way of handling such an extensive set of data, while still allowing for a (semi)quantitative study. There are limitations to such an approach, mainly: the accuracy of the model, its complexity (always drastically lower than in reality), low availability of consistent experimental input data, etc. Let us mention the correct of Na-K exchanger stoichiometry 3:1, based on simulations prediction as early as 1985. Let us mention the correct of Na-K exchanger stoichiometry 3:1, based on simulations prediction as early as 1985. [1]
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