Control of cardiac performance by Ca-turnover.

A quantitative model of Ca-turnover in cardiac cells that incorporates negative feedback modulation of sarcolemmal calcium transport (via Ca channels and Na/Ca exchange) has been designed. The Na/Ca exchange current was expressed as INaCa = INaCar + delta INaCa. The component INaCar reflects slow changes of Ca2+ and Na+ concentrations and depends on the Na/K pump. delta INaCa is the fast component related to the Ca2+ transient. The single input to the model is an arbitrary sequence of intervals between excitations; outputs are sequences of calcium amounts transferred among the compartments during individual intervals. The model operates with a combination of discrete variables (amounts of Ca transferred during contraction, relaxation and rest) and continuous variables - slow changes in ionic concentrations. Since the model is not formalistic but respects the nature of the underlying elements of the system, it enables us to stimulate the known effects of cardiotropic drugs or to predict their unknown mechanisms by visualizing the changes in individual Ca compartments. By altering the parameters, the model also stimulates the known species and tissue differences in rate-dependent phenomena.