Jaeger, Karoline Horgmo published the artcileImproved computational identification of drug response using optical measurements of human stem cell derived cardiomyocytes in microphysiological systems, Product Details of C17H18N2O6, the main research area is microphysiol system human stem cell optical measurement; cardiac action potential model; cardiac ion channel blockade; computational identification of drug response; computational inversion; computational maturation; human induced pluripotent stem cell derived cardiomyocytes; voltage sensitive dye.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) hold great potential for drug screening applications. However, their usefulness is limited by the relative immaturity of the cells’ electrophysiol. properties as compared to native cardiomyocytes in the adult human heart. In this work, we extend and improve on methodol. to address this limitation, building on previously introduced computational procedures which predict drug effects for adult cells based on changes in optical measurements of action potentials and Ca2+ transients made in stem cell derived cardiac microtissues. This methodol. quantifies ion channel changes through the inversion of data into a math. model, and maps this response to an adult phenotype through the assumption of functional invariance of fundamental intracellular and membrane channels during maturation. Here, we utilize an updated action potential model to represent both hiPSC-CMs and adult cardiomyocytes, apply an IC50-based model of dose-dependent drug effects, and introduce a continuation-based optimization algorithm for anal. of dose escalation measurements using five drugs with known effects. The improved methodol. can identify drug induced changes more efficiently, and quantitate important metrics such as IC50 in line with published values. Consequently, the updated methodol. is a step towards employing computational procedures to elucidate drug effects in adult cardiomyocytes for new drugs using stem cell-derived exptl. tissues.
Frontiers in Pharmacology 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, Product Details of C17H18N2O6.