Action Potential Duration (APD) Testing on Stem Cell-Derived Human Cardiomyocytes
high sensitivity, physiologically relevant, predictive
Stem cell-derived human cardiomyocytes (SC-hCMs) provide a unique opportunity to study drug effects on human ventricular-type myocytes, cells which are not typically available for routine testing. Use of SC-hCMs provides a significant improvement over current methodologies by offering better correlation between pre-clinical and clinical studies, higher throughput screening, rapid turnaround time, and cost savings in an animal-free assay. |
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The SC-hCM APD Assays Delivers:
- Detection of AP Prolongation (QT risk) and EADs (trigger for Torsades de Pointes)
- Stable recordings at physiological temperature with minimal diffusion delays
- Cost-effective compared to conventional methodologies
- Human test system
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| Figure 1: SC-hCM APD prolongation and EADs induced by sotalol. A) SC-hCM action potentials (APs) recorded before and after ~10 minute exposure to hERG (IKr) blocker sotalol. In addition to prolonging the APD (a surrogate biomarker for QT prolongation), sotalol induced early afterdepolarizations (EADs), a precursor to cardiac arrhythmias such as Torsades de Pointes. B) Typical time course of the effect of sotalol on APs of SC-hCM and rabbit Purkinje fiber (PF). Upper trace: rabbit PF. Lower trace: SC-hCM. Steady-state response to application of sotalol was observed after approximately 5 minutes in the SC-hCM assay, but required more than 15 minutes in the rabbit PF assay. C) Overlay of representative SC-hCM APs in vehicle control and after exposure to sotalol. |
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Terfenadine1 |
1 µM |
False Negative |
0.03 µM1 |
0.004 |
Quinidine1 |
1 µM |
1 µM |
0.3 µM1 |
0.83 |
Cisapride1 |
0.1 µM |
0.1 µM |
0.01 µM1 |
0.026 |
Sotalol |
10 µM |
100 µM |
10 µM |
268 |
Verapamil |
10 µM |
1 µM |
1 µM |
0.125 |
Chromanol 293B1 |
False Negative |
False Negative |
300 µM1 |
10.74 |
E- 4031 |
N/A |
0.01 µM |
0.01 µM |
0.011 |
Nifedipine1 |
N/A |
> 10 µM |
0.03 µM1 |
N/A |
- Orange indicates increased sensitivity of SC-hCMs compared to PF
- Positive indicates APD90 change
≥10%
- From manual patch clamp experiments on hERG ion channels expressed in HEK cells
- From KvLQT/minK ion channels expressed in HEK cells (Chromanol 293B
blocks KvLQT/minK, not hERG)
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Additional information:
Frequently asked questions about the SC-hCM APD Assay
Publication: The action potential and comparative pharmacology of stem cell-derived human cardiomyocytes. Peng S, Lacerca AE, Kirsch GE, Brown, AM, Bruening-Wright A. 2010. 61(3):277-286. J Pharmacol Toxicol Methods.
For a quote or additional information, please email inquiries@chantest.com or call 216-332-1665. |
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