Collaborative Activities with Cellular Dynamics
Neurons - "Electrophysiological recordings of LGIC and AA transporters in iCell® GlutaNeurons"
Patchliner,
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) and
SURFE2R N1 application note:
(0.5 MB)
Cells were kindly provided by FUJIFILM Cellular Dynamics, Inc.
NaV1.5-Late - "INa-Late recorded from CHO cells and hiPSC-CMs on Nanion´s Patchliner"
Patchliner application note:
(0.5 MB)
Cells were kindly provided by Charles River.
iCell® Cardiomyocytes2 were kindly provided by Fujifilm Cellular Dynamics International.
NCX1 - Effect of block of cardiac NCX on beat rate
CardioExcyte data and applications:
Cells were kindly provided by Cellular Dynamics.
Block of NCX1 expressed in iCell® Cardiomyocytes2 by SEA 0400 caused a dose dependent increase in beat rate.
NCX1 - Current traces recorded from Cor.4U Cardiomyocytes, iCell Cardiomyocytes and HEK cells
SURFE2R N1 data and applications:
Cardiac NCX1 was activated using 30 μM Ca2+ on the SURFE2R N1. NCX1 was recorded from Cor.4U® Cardiomyocytes, iCell® Cardiomyocytes2 or overexpressed in HEK cells. The calcium affinity was determined for NCX1 recorded from iCell® Cardiomyocytes2 and HEK cells, shown on the right.
NCX1 - Block by KB-R7943
SURFE2R N1 data and applications:
Cardiac NCX1 expressed in iCell® Cardiomyocytes2, Cor.4U® Cardiomyocytes or HEK cells was blocked by increasing concentrations of KB-R7943.
NCX1 - Block by SEA0400
SURFE2R N1 data and applications:
Cardiac NCX1 expressed in iCell® Cardiomyocytes2 or HEK cells was blocked by increasing concentrations of SEA0400, a specific blocker of NCX.
2018 - Expression and pharmacology of GluA2-containing AMPA receptors in cell lines and stem cell-derived neurons
Port-a-Patch,
Patchliner and
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) poster, Europhysiology Meeting 2018
(0.9 MB)
2018 - Combining electrophysiology and contractility recordings for more complete assessment of hiPSC-CMs
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384),
Patchliner and
CardioExcyte 96 poster, Europhysiology Meeting 2018
(1.4 MB)
2018 - A Sensor Based Technique for Pharmacological Safety Testing of Cardiac Transport Proteins NCX, NaKATPase and Respiratory Chain Complexes
CardioExcyte 96 and
SUFE²R 96SE poster, SPS 2018
(1.7 MB)
2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) and
Patchliner poster, FENS Meeting 2018
(2.5 MB)
2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp
SyncroPatch 384PE (a predecessor model of the SyncroPatch 384) and
Patchliner poster, BPS Meeting 2017
(1.7 MB)
2018 - Cross-site comparison of excitation-contraction coupling using impedance and field potential recordings in hiPSC cardiomyocytes
CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2018)
Authors:
Bot C.T., Juhasz K., Haeusermann F., Polonchuk L., Traebert M., Stölzle-Feix S.
Cardiac Ion Channels - Pharmacology of Vandetanib
CardioExcyte 96 and
Patchliner data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.
The image on the left hand side displays the results of the blocking effect of Vandetanib on hERG, NaV1.5, CaV1.2 and KV4.3. The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 1 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility.
Cardiac Ion Channels - Pharmacology of Sotalol
CardioExcyte 96 and
SyncroPatch 384PE (a predecessor model of SyncroPatch 384) data and applications:
Cells were kindly provided by Charles River and Cellular Dynamics.
The image on the left hand side displays the results of the blocking effect of Sotalol on hERG. The result is in good agreement with manual patch clamp data (Crumb et al., 2016). The compound induced arrhythmia when iPSC-CM were exposed to a minimum concentration of 10 µM. Arrhytmic events were both detected in field potential recordings as well as in the impedance based contractility measurements.
2017 - Cross-site comparison of myocyte phase II compounds on different iPS cardiomyocytes based on CardioExcyte 96 recordings
CardioExcyte 96 presentation (slide deck)
(2.2 MB)
2017 - HTS in Cardiac Safety
CardioExcyte 96 presentation (slide deck)
(4.0 MB)
Cardiomyocytes - "Impedance and EFP recordings of iCell Cardiomyocytes² on the CardioExcyte 96"
CardioExcyte 96 Application Note
(2.8 MB)
Cells were kindly provided by Cellular Dynamics.
2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) publication in Journal of Lab Automation (2016)
Authors:
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.
2015 - Novel screening techniques for ion channel targeting drugs
Patchliner,
SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and
CardioExcyte 96 publication in Channels (2015)
Authors:
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.
2012 - Characterizing Human Ion Channels in Induced Pluripotent Stem Cell-Derived Neurons
Patchliner publication in Journal of Biomolecular Screening (2012)
Authors:
Haythornthwaite A, Stoelzle S, Hasler A, Kiss A, Mosbacher J, George M, Brüggemann A, Fertig N.
2013 - Minimized cell usage for stem cell-derived and primary cells on an automated patch clamp system
Patchliner publication in Journal of Pharmacological and Toxicological Methods (2013)
Authors:
Becker N., Stoelzle S., Göpel S., Guinot D., Mumm P., Haarmann C., Malan D., Bohlen H., Kossolov E., Kettenhofen R., George M., Fertig N., Brüggemann A.
2015 - New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings.
CardioExcyte 96 publication in Journal of Laboratory Automation (2015)
Authors:
Doerr L., Thomas U., Guinot D.R., Bot C.T., Stoelzle-Feix S., Beckler M., George M., Fertig N.
GABAA Receptor - Currents in iCell Neurons
Patchliner data and applications:
Cells were kindly provided by Cellular Dynamics.
Activation of GABAA receptor currents by 30 μM GABA and partial block of the current response by 1 μM bicuculline. Bicuculline was pre-applied for at least 30 s before co-application with GABA (30 μM). Approximately 50% of the current was blocked by 1 μM bicuculline.
Neurons (iPSC-derived) - Voltage Gated Potassium Currents
Patchliner data and applications:
Cells were kindly provided by Cellular Dynamics.
A Voltage-gated K+ current recorded in iCell® neurons. Current responses to a voltage step protocol. An outward K+ current can be seen in this cell.
B Corresponding IV plot from an average of 7 cells.
Neurons (iPSC-derived) - TXX Block of Sodium Currents
Patchliner data and applications:
Cells were kindly provided by Cellular Dynamics.
A Block of Na+ current by increasing concentrations of TTX. Current was blocked by low nM concentrations of TTX indicating a TTX sensitive Na+ channel type expressed in this cell.
B Concentration response curve for TTX inhibition, IC50 = 4.9 nM (n =1).
Neurons (iPSC-derived) - Voltage-Gated Sodium Currents
Patchliner data and applications:
Cells were kindly provided by Cellular Dynamics.
Voltage-gated Na+ current recorded in iCell® Neurons. Current responses to a voltage step protocol.
A large inward Na+ current can be seen in this cell with a K+ outward current present at positive voltages.
B Normalised IV plot from an average of 4 cells.
Neurons - "Stem cell-derived neurons recorded on Nanion's Patchliner"
Patchliner application note:
(0.4 MB)
Cells were kindly provided by Cellular Dynamics.
Cardiac Action Potentials - Automated recordings from iCells
Patchliner data and applications:
The stem cell-derived cardiomyocytes (iCell) were kindly supplied by Cellular Dynamics.
In this example both Na+ and Ca2+ mediate the action potential. When nifedipine is applied in the current clamp mode, the action potential is shortened significantly due to block of the calcium channels.
Effect of Isoproterenol
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Isoproterenol is enhancing contractile force. Upon application of increasing Isoproterenol concentrations a beating frequency increase is observed, along with an increased beating amplitude (positive force-frequency relationship).
Isoproterenol increases contraction force
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Amplitude increase of contraction signals as % of control plotted against increasing Isoproterenol concentrations.
Kinase inhibitors – Chronic compound effects on cardiomyocytes
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Here Structural and/or functional toxicity of Kinase inhibitors Trametinib, Sorafenib, Nilotinib and A-674563 was investigated. Compound incubation time was 5 days.
During investigations of chronic effects it could take days and weeks until onset of adverse effects. The CardioExcyte and FLEXcyte technology and the consumables are perfectly suited for such studies.
Kinase inhibitor Nilotinib – Arrhythmogenic effects on cardiomyocytes
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Exemplary arrhythmia as observed 24 h after application of Kinase inhibitor Nilotinib. Aftercontractions (regular intervals and irregular intervals) and beat rate variability were observed.
Kinase inhibitor Gefitinib – Arrhythmogenic effects on cardiomyocytes
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Exemplary arrhythmia as observed 24 h after application of Kinase inhibitor Gefitinib. Aftercontractions (regular intervals and irregular intervals) and Fibrillations were observed, respectively.
Kinase inhibitor A-674563 – Arrhythmogenic effects on cardiomyocytes
FLEXcyte 96 data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics.
Exemplary arrhythmia as observed 24 h after application of Kinase inhibitors A-674563. Aftercontractions (regular intervals and irregular intervals) were observed.
Cardiomyocytes - Data from different cell providers
CardioExcyte data and applications:
Cells were kindly provided by FUJIFILM Cellular Dynamics, Nexel, Ncardia, Axiogenesis, Pluriomic, GE Healthcare, ReproCell, Takara Bio Cellartis Clonetech.
The CardioExcyte 96 allows for
• Non-invasive, label-free measurements of beating cardiomyocyte networks
• 96 recording wells in parallel with 1 ms time resolution
• Quick experiments or long-term compound effects on cardiotoxicity
• Real-time access to beating parameters
• Outstanding software for data analysis and export
• Cost effcient consumables - 96-well format
Cardiomyocytes - Effect of E4031 on the impedance and EFP signals on iCell cardiomyocytes
CardioExcyte data and applications:
Cells were kindly provided by Cellular Dynamics.
Effect of the specific hERG blocker, E4031, on the impedance and EFP signals. A Impedance signal of 12 wells in control conditions (left) and the same 12 wells after 13 mins incubation in E4031 at the concentrations indicated (right). E4031 (300 nM, 3 mins incubation) induces EAD, shown in the inset, which can lead to potentially fatal ventricular arrhythmias. B EFP signal of 12 wells in control conditions (left) and the same 12 wells after 13 mins incubation in E4031 at the concentrations indicated (right). E4031(300 nM, 30 mins incubation) also causes arrhythmic effects in the EFP mode shown in the inset.
Cardiomyocytes - Effect of the ß-adrenergic receptor agonist, Isoproterenol, on the impedance and EFP signals on iCells
CardioExcyte data and applications:
Cells were kindly provided by Cellular Dynamics.
A Impedance signal of 12 wells in control conditions (left) and the same 12 wells after 13 mins incubation in isoproterenol at the concentrations indicated. Isoproterenol acts as a heart stimulant, it increases heart rate, an effect which is highlighted in the inset where the trace in the presence of isoproterenol (300 nM; black) and the control trace (red) are shown overlaid. In the presence of even low concentrations of isoproterenol (1 nM), an increase in the beat rate is observed. B Bar graph showing beat rate before (dark blue) and after (light blue) incubation in isoproterenol at the concentrations indicated. At all concentrations, a clear increase in beat rate is observed. C EFP signal of 12 wells in control conditions (left) and the same 12 wells after 30 mins incubation in isoproterenol at the concentrations indicated (right). Isoproterenol shortens the FPD, an effect which is highlighted in the inset where the trace in the presence of isoproterenol (300 nM; black) and the control trace (red) are shown overlaid.