Role of Submembrane Spaces in the Control of Transmembrane Ion Flux and Cellular Inotropic State in a Model of Human Ventricular Cardiomyocyte

We have recently developed a model of human ventricular cardiomyocyte incorporating the t-tubular and surface submembrane spaces and restricted ion exchange between these spaces and cytosol.After incorporating the experimental finding that majority of Na + -Ca 2+ exchanger proteins are located at the t-tubular membrane of human ventricular cardiomyocytes, we explored the consequences of ion concentration changes in the submembrane spaces on the electrophysiological activity of these cells.Consistently with the experimental and modelling studies published so far, our model predicts an increased Ca 2+ extrusion during the action potential.However, our model also predicts a significant reduction of Ca 2+ extrusion throughout the diastole, which can ultimately lead to an increase of cellular inotropy.