Pfeiffer-Kaushik, Emily R. published the artcileElectrophysiological characterization of drug response in hSC-derived cardiomyocytes using voltage-sensitive optical platforms, Quality Control of 21829-25-4, the main research area is arrhythmia cardiomyocyte nifedipine mexiletine voltage sensitive optical sensor; Action potential; Cardiac electrophysiology; Comprehensive in vitro proarrhythmia assay (CiPA); ICH S7B; Methods; Safety pharmacology; Stem cell-derived cardiomyocyte; Torsades de pointes (TdP) arrhythmia; Voltage-sensitive optical sensors; hERG.
Voltage-sensitive optical (VSO) sensors offer a minimally invasive method to study the time course of repolarization of the cardiac action potential (AP). This Comprehensive in vitro Proarrhythmia Assay (CiPA) cross-platform study investigates protocol design and measurement variability of VSO sensors for preclin. cardiac electrophysiol. assays. Three com. and one academic laboratory completed a limited study of the effects of 8 blinded compounds on the electrophysiol. of 2 com. lines of human induced pluripotent stem-cell derived cardiomyocytes (hSC-CMs). Acquisition technologies included CMOS camera and photometry; fluorescent voltage sensors included di-4-ANEPPS, FluoVolt and genetically encoded QuasAr2. The exptl. protocol was standardized with respect to cell lines, plating and maintenance media, blinded compounds, and action potential parameters measured. Serum-free media was used to study the action of drugs, but the exact composition and the protocols for cell preparation and drug additions varied among sites. Baseline AP waveforms differed across platforms and between cell types. Despite these differences, the relative responses to four selective ion channel blockers (E-4031, nifedipine, mexiletine, and JNJ 303 blocking IKr, ICaL, INa, and IKs, resp.) were similar across all platforms and cell lines although the absolute changes differed. Similarly, four mixed ion channel blockers (flecainide, moxifloxacin, quinidine, and ranolazine) had comparable effects in all platforms. Differences in repolarization time course and response to drugs could be attributed to cell type and exptl. method differences such as composition of the assay media, stimulated vs. spontaneous activity, and single vs. cumulative compound addition In conclusion, VSOs represent a powerful and appropriate method to assess the electrophysiol. effects of drugs on iPSC-CMs for the evaluation of proarrhythmic risk. Protocol considerations and recommendations are provided toward standardizing conditions to reduce variability of baseline AP waveform characteristics and drug responses.
Journal of Pharmacological and Toxicological Methods 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, Quality Control of 21829-25-4.