Kernik, Divya C. published the artcileA computational model of induced pluripotent stem-cell derived cardiomyocytes incorporating experimental variability from multiple data sources, Application In Synthesis of 21829-25-4, the main research area is Pluripotent stem cell cardiomyocyte electrophysiol; computer modelling; iPSC-CMs; variability.
A promising in vitro method to address patient-specific proclivity to cardiac disease utilizes induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We postulated, however, that cell-to-cell variability may constitute a strength when appropriately utilized in a computational framework to build cell populations that can be employed to identify phenotypic mechanisms and pinpoint key sensitive parameters. Thus, we have exploited variation in exptl. data across multiple laboratories to develop a computational framework for investigating subcellular phenotypic mechanisms. We have developed a whole-cell model of iPSC-CMs composed of simple model components comprising ion channel models with single exponential voltage-dependent gating variable rate constants, parameterized to fit exptl. iPSC-CM data for all major ionic currents. By optimizing ionic current model parameters to multiple exptl. datasets, we incorporate exptl.-observed variability in the ionic currents. The resulting population of cellular models predicts robust inter-subject variability in iPSC-CMs. This approach links mol. mechanisms to known cellular-level iPSC-CM phenotypes, as shown by comparing immature and mature subpopulations of models to analyze the contributing factors underlying each phenotype. In the future, the presented models can be readily expanded to include genetic mutations and pharmacol. interventions for studying the mechanisms of rare events, such as arrhythmia triggers.
Journal of Physiology (Oxford, United Kingdom) published new progress about Action potential. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.