FBS Colloquia No.207Physiological Laboratory

Reproducing cardiac function spatiotemporally using biological simulator

Heart keeps beating continuously to pump out blood to supply the whole body. For the heart to keep pumping blood rhythmically, it is important that the pacemaker cells in sinoatrial node activates spontaneously and working cardiomyocytes in atriums and ventricles contract in response to the electrical stimulation propagated from the sinoatrial node. All these functions are generated by the intracellular ion mechanisms. As the intracellular and the extracellular space is insulated by a lipid bilayer membrane, ions only traverse the cell membrane through ionic channels and transporters. There are tens of kinds of ion channels and transporters expressed in a cell membrane, and their density and distribution characterize the electrical activity of the cell. In addition, activity of each channel and transporter is regulated by membrane potential or intracellular and extracellular ion concentrations, interacts with each other and changes with time. Therefore it is almost impossible to estimate the magnitude of each current component at a certain time and discuss its contribution to the dynamic function quantitatively without computation. Therefore, we developed a cardiac cell model that reconstructs the electrical activity of the cells by formulating each current component by ion channels and transporters and integrating them. Since the changes of all parameters are calculated, it is possible to quantitatively understand the ionic mechanisms using the model. We also developed a circulation model that can reproduce the cardiac cycle utilizing the contractile force generated by the cell model as a driving force. In the presentation, I will introduce the background experimental data, explain the model formation according to the data and reproduce the data by simulation experiment. The dynamism of the cardiac function is presented by running simulators from time to time throughout the presentation.