Computer Insight into the Molecular Level of Heart Failure. What is the Role of NCX?

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.