in vitro repolarization assay
hiPSC-derived cardiomyocytes Assays
We use manual patch clamp to detect drug-induced changes in action potential morphology recorded from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Changes in the various phases of the action potential reflect the integrated drug effects on one or multiple ion channels. Abnormal repolarization under the form of early after depolarizations (EADs) or delayed after depolarizations (DADs) is an indication of proarrhythmia liability.
Assay parameters include:
- Action potential duration (e.g.,APD50, APD90)
- Upstroke amplitude
- Maximum Diastolic Potential
- Incidence of EADs or DADs
- Dose response curves
- Response to various stimulation frequencies
- Custom assays to suit client needs
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Nonclinical strategy for assessing risk of delayed ventricular repolarization and development of torsades de pointe
A mechanistic understanding of the generation of torsades de pointe (TdP) and the development of new physiologically relevant assays have made it possible to obtain more information from nonclinical assays to predict TdP risk. Because the cardiac action potential results from the orchestrated opening and closing of multiple ion channels in a time- and voltage-dependent manner, an integrative approach is required. The in vitro hERG assay and in vivo QT assay, combined with additional cardiac ionic currents and cellular repolarization assays including the hiPSC-CM assay can be used for risk assessment of drug-induced proarrhythmia. As hERG block can be offset by inhibition of inward sodium or calcium currents, testing additional ion channels can therefore inform on the risk of developing TdP. To confirm potential effects on repolarization and risk of developing arrhythmias, drug-induced effects on action potentials recorded from hiPSC-CM can be determined.
Talk to Us About Your Research Needs
Call 1.604.827.1733