Control over action potential, calcium peak and average fluxes in the cyclic quasi-steady-state ion transport system in cardiac myocytes: in silico studies

MCA (metabolic control analysis) was originally developed to deal with steady-state systems. In the present theoretical study, the control analysis is applied to the cyclic quasi-steady-state system of ion transport in cardiac myocytes. It is demonstrated that the metabolic control of particular components (channels, exchangers, pumps) of the system over such quasi-steady-state variables as action potential amplitude, action potential duration, area under the Ca2+ peak and average fluxes through particular channels during one oscillation period can be defined and calculated. It is shown that the control over particular variables in the analysed, periodical system is distributed among many (potentially all) components of the system. Nevertheless, some components seem to exert much more control than other components, and different variables are controlled to the greatest extent by different channels. Finally, it is hypothesized that the Na+ and K+ transport system exerts a significant control over the Ca2+ transport system, but not vice versa.