EFFECT OF ION CONCENTRATION CHANGES IN T-TUBULES ON INTRACELLULAR SIGNALS CONTROLLING MECHANICAL ACTIVITY IN A MODEL OF HUMAN VENTRICULAR CARDIOMYOCYTE
|Year of publication
|Article in Periodical
|Magazine / Source
|MU Faculty or unit
|human heart; cardiac cell; t-tubule; quantitative modeling
|The transverse (t-) tubular system serves to bring electrical signals deep inside the muscle cells to control mechanical responses. Our preliminary mathematical model of human ventricular cardiomyocyte incorporating t-tubular system  was improved by introducing description of latest experimental data related to morphology of human t-tubules and to specific properties of ionic currents. To describe the ion diffusion within t-tubular lumen, we partitioned the t-tubule compartment into nine concentric cylindrical segments. Using the model, we studied the effect of activity-induced concentration changes in the t-tubules on Ca2+ entry into the cell and the intracellular Ca2+ transients controlling the strength of cellular contraction. The values of some crucial parameters, unknown in human cardiomyocytes to date, were regarded as independent variables. The simulations confirmed the tendency of the activity-induced t-tubular concentration changes of Ca2+ to reduce the Ca2+ entry into the cell as well as the intracellular Ca2+ transient. The effect rose with the increase of t-tubular fraction of L-type Ca2+ channels (fCa,t), with the decrease of t-tubular fraction of Ca2+ pump (fpCa,t) and with the increase of the time constant of Ca2+ exchange between external space and t-tubule lumen.