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Pacing of cardiomyocytes

The capability to pace hiPSC-derived cardiomyocytes at user-defined beat rates enables more precise and in-depth analysis of cardioactive compound effects. As an advantage, beat rate dependent effects (i.e. (reverse) use-dependence) can be measured in a physiological relevant way with reduced variability from well-to-well.

User guide

Pluricyte® Cardiomyocytes are validated for electrical pacing using Maestro™ E-Stim+ MEA technology

Ncardia has validated the combination of Pluricyte® Cardiomyocytes with E-Stim+ MEA technology for the Maestro™ MEA system (Axion BioSystems) in-house. This combination provides you with a highly relevant in vitro assay to study cardiac safety profiles of compounds under stable and defined pacing rates at an early stage of drug development. Compared to assays using spontaneous beating cardiomyocytes, this next generation assay provides several advantages:

  • Assessment of cardiac safety at user-defined beat rates
  • Detection of beat rate dependent effects (i.e. (reverse) use-dependence)
  • Increased physiological relevance
  • Reduced well-to-well and assay-to-assay variability

You can find a step-by-step description of studying drug effects during stimulation of Pluricyte® Cardiomyocytes using the E-Stim+ Classic MEA 48 plate in our User Guide.  

Characteristics of Pluricyte® Cardiomyocytes during electrical stimulation

Pluricyte® Cardiomyocytes quickly adapt their physiology to new pacing rates applied through the Maestro™ MEA system.

Application

Cardiac safety assessment using electrically paced Pluricyte® Cardiomyocytes in combination with Maestro™ E-Stim+ MEA technology

In this electrical pacing assay Pluricyte® Cardiomyocytes adapt to beat rates applied by external stimuli, like in the in vivo situation where the ventricles depend on external input from pacemaker cells. An advantage of pacing is that (reverse) use-dependence of drugs can be tested. This phenomenon, also known as beat rate dependent drug effects, is observed with several types of ion channel modulators. Below, an example is shown of reverse use dependence of E4031 (a hERG channel blockers) and use dependence of TTX (a sodium channel blocker) in electrically paced Pluricyte® Cardiomyocytes.

Reverse use-dependence of E4031 in Pluricyte® Cardiomyocytes

Reverse use-dependent effect of hERG channel blocker E4031 on the field potential duration of Pluricyte® Cardiomyocytes paced at 0.5-1.25 Hz.

Use-dependence of TTX in Pluricyte® Cardiomyocytes

Use-dependent effect of sodium channel blocker TTX on the spike amplitude of Pluricyte® Cardiomyocytes paced at 0.5-1.25 Hz

Download the complete application note here: