%0 Journal Article %1 Sawada2014 %A Sawada, Kohei %A Taniguchi, Tomohiko %A Ojima, Atsuko %A Yoshinaga, Takkashi %A Miyamoto, Norimasa %A Szkolnicka, Dagmara %A Farnworth, Sarah %A Lucendo-Villarin, Balta %A Storck, Chris %A Zhou, Wenli %A Iredale, John %A Flint, Oliver %A Hay, David %D 2014 %J Journal of Pharmacological and Toxicological Methods %K imported %R 10.1016/j.vascn.2014.03.159 %T Optimization and pharmacological characterization of iCell cardiomyocytes for electrophysiological assessment in a multi-electrode extracellular recording system Accurate prediction of drug induced liver injury using stem cell based approaches %X 30 nM, but the beating rate increased and reached to about twice the basal rate at 300 nM. Isoproterenol increased both contraction and relaxation velocity and beating frequency. From these results, it is concluded that the laser-speckle contrast technique is useful for the analysis of the effects of compounds on contractile function. iPS cell derived cardiomyocytes have become a valuable tool for safety assessment in drug discovery. In order to translate the results obtained in these cells into in vivo effects in humans, basic phys-iological or pharmacological properties of these cells should be well characterized. Present studies examined the effects of temperature, cell density and representative ion channel modulators with MED64 in iCell cardiomyocytes. When the experimental temperature was changed from 35 to 38.5 °C, the corrected field potential duration (FPDc) decreased from 370 to 285 msec (24 msec/°C) almost linearly, but beating rate increased from 42 to 66 bpm at 37 °C and did not increase further even at 38.5 °C. The cell density of plating affected the response to Iks blockers. The concentration–response curves for 293B and HMR1556 shifted to the right when cell densities were decreased from 30,000, 15,000 and 7500 cells/well. In lower density conditions, cell sizes enlarged and expression of the KCNQ1 gene decreased. The hERG channel blocker, E4031, consistently prolonged the FPDc at concentrations higher than 3 nM regardless of the cell density. A calcium channel blocker, verapamil, decreased the FPDc concentration-dependently at concentrations 30 nM and above, but increased the beating rate significantly at the same concentrations. The If channel blocker, ZD7288 decreased the beating rate in a concentration-dependent manner at 0.3 mM and above. Sodium and T-type calcium channel blockers also had some effects. These results indicate that the basic information on experimental conditions and pharmacological effects is very important for transla-tion of the data. Background: Despite major progress in the knowledge and management of human liver disease, there are in excess of 29 million people in the European Union estimated to suffer from chronic liver morbidities. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation which is limited by donor organ

@article{Sawada2014, abstract = {30 nM, but the beating rate increased and reached to about twice the basal rate at 300 nM. Isoproterenol increased both contraction and relaxation velocity and beating frequency. From these results, it is concluded that the laser-speckle contrast technique is useful for the analysis of the effects of compounds on contractile function. iPS cell derived cardiomyocytes have become a valuable tool for safety assessment in drug discovery. In order to translate the results obtained in these cells into in vivo effects in humans, basic phys-iological or pharmacological properties of these cells should be well characterized. Present studies examined the effects of temperature, cell density and representative ion channel modulators with MED64 in iCell cardiomyocytes. When the experimental temperature was changed from 35 to 38.5 °C, the corrected field potential duration (FPDc) decreased from 370 to 285 msec (24 msec/°C) almost linearly, but beating rate increased from 42 to 66 bpm at 37 °C and did not increase further even at 38.5 °C. The cell density of plating affected the response to Iks blockers. The concentration–response curves for 293B and HMR1556 shifted to the right when cell densities were decreased from 30,000, 15,000 and 7500 cells/well. In lower density conditions, cell sizes enlarged and expression of the KCNQ1 gene decreased. The hERG channel blocker, E4031, consistently prolonged the FPDc at concentrations higher than 3 nM regardless of the cell density. A calcium channel blocker, verapamil, decreased the FPDc concentration-dependently at concentrations 30 nM and above, but increased the beating rate significantly at the same concentrations. The If channel blocker, ZD7288 decreased the beating rate in a concentration-dependent manner at 0.3 mM and above. Sodium and T-type calcium channel blockers also had some effects. These results indicate that the basic information on experimental conditions and pharmacological effects is very important for transla-tion of the data. Background: Despite major progress in the knowledge and management of human liver disease, there are in excess of 29 million people in the European Union estimated to suffer from chronic liver morbidities. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation which is limited by donor organ}, added-at = {2019-06-18T22:58:43.000+0200}, author = {Sawada, Kohei and Taniguchi, Tomohiko and Ojima, Atsuko and Yoshinaga, Takkashi and Miyamoto, Norimasa and Szkolnicka, Dagmara and Farnworth, Sarah and Lucendo-Villarin, Balta and Storck, Chris and Zhou, Wenli and Iredale, John and Flint, Oliver and Hay, David}, biburl = {https://www.bibsonomy.org/bibtex/2fcf5ff4664c8028cce69f17fce894bb1/fcdi}, doi = {10.1016/j.vascn.2014.03.159}, interhash = {4746a19b071247a52e4156290e5f5b26}, intrahash = {fcf5ff4664c8028cce69f17fce894bb1}, journal = {Journal of Pharmacological and Toxicological Methods}, keywords = {imported}, timestamp = {2019-06-18T22:58:43.000+0200}, title = {{Optimization and pharmacological characterization of iCell cardiomyocytes for electrophysiological assessment in a multi-electrode extracellular recording system Accurate prediction of drug induced liver injury using stem cell based approaches}}, year = 2014 }