C. A. Otto, D. U. J. Keller, O. Dössel, and G. Seemann. Integrating Beta-Adrenergic Signaling into a Computational Model of Human Cardiac Electrophysiology. In IFMBE Proceedings World Congress on Medical Physics and Biomedical Engineering, vol. 25/4, pp. 1033-1036, 2009
Student Theses (1)
C. A. Otto. Impact of adrenergic regulation on the electrophysiological properties of human ventricular myocytes. Institut für Biomedizinische Technik, Karlsruher Institut für Technologie (KIT). Diplomarbeit. 2009
Abstract:
We presented a model of human ventricular myocytes that includes a description of beta-adrenergic regulation. Furthermore we investigated the impact of interacting components in the signaling net- work on cellular electrophysiology. Three main target proteins that undergo phosphorylation have been considered (ICaL, Iup, IKs). Parameters from Saucermans model that describe the conditions in the species rat have been adapted for human ventricular tissue where possible. Simulations for endo-, midmyocardial and epicardial cells were conducted. The influence of beta-adrenergic cell stimulation on currents, ion concentrations, gating variables and action potentials was investigated and compared with Saucermans results.A faster and increased ICaL triggers a higher influx of calcium into the cytosol. The larger amount of free calcium in the cytosol has to be pumped back into the SR at a higher rate which is enabled due to PLB phosphorylation and thus indirect strengthening of Iup. For heart rate adaption to a higher frequency, the APD has to be shortened where the increase in IKs is a major factor. The adapted ion channels lead to a modification of the transmembrane voltage and ion concentrations in the cytosol which then influence all other ion channels. The simulation results were comparable to the results of Saucerman [62] which were based on a modified Luo-Rudy model. As beta-adrenergic stimulation strongly increases the cytosolic calcium concentration, it will also be an important factor when simulating the mechanical properties of a myocyte.