In this paper, we present a novel quantitative description of intracellular and t-tubular Ca2+ dynamics in a model of rat cardiac ventricular myocyte. In order to simulate recently published data, the model incorporates t-tubular and peripheral dyads and intracellular subspaces, segmentation of the t-tubular luminal volume, reformulation of the inactivation properties of t-tubular land peripheral L-type calcium current (ICa) and a description of exogenous Ca2q+ buffer function in the intracellular space. The model is used to explore activity-induced changes of ion concentration in the intracellular and t-tubular spaces and their role in excitation - contraction coupling in ventricular myocytes. and Obsahuje Appendix se seznamy literatury, užitých zkratek a symbolů
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 [1] 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 (TCa,extt). Significant effect simultaneously fCa,t ≥ 0.64, fpCa,t ≤ 0.2 and TCa,extt ≥ 240 ms. and Obsahuje Appendix se seznamy literatury, užitých zkratek a symbolů