CardioFlux - Cor.4U calcium transient analysis

 

Cells Cor.4U®  / vCor.4U®  cardiomyocytes or co-cultures of cardiomyocytes with FibroCor.4U cardiac fibroblasts
Cell source Human iPS cells of 26y/o Caucasian female
Service type       Functional / phenotypic analysis
Delivery

 A study protocol will be sent to initiate the study. Results are sent as draft and final study report

Timeline

Experimental run time: ~1.5 weeks per plate. Draft report: within 5 weeks.

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ADVANTAGES 

  • Cost-effective, robust and fast assay to assess toxicity/efficacy early in drug development
  • Combines Cor.4U® , a well-characterized predictive cardiac model, with HTS capabilities
  • Highly validated assay; part of the CiPA (Comprehensive in Vitro Proarrhythmia Assay) initiative

 

 

 

CardioFlux calcium transient analysis using cor4UCalcium transient analysis using Cor.4U®   on the Hamamatsu FDSS®  kinetic plate reader enhances assessment of cardiac liability and drug efficacy while lowering costs per data point via 384-well format.

 

Technology overview 

CardioFlux utilizes intracellular calcium transients and beat rate analysis of Cor.4U®  human induced pluripotent stem (iPS) cell-derived cardiomyocytes to assess cardiac liability and efficacy of drug compounds.

Transient rise of cytosolic free calcium ion concentrations ([Ca2+ ]) plays a pivotal role in cardiomyocyte contraction. During the cardiac action potential, the rise and duration of these calcium transients [Ca2+ ] are carefully controlled by a mechanism called the calcium-induced calcium release. 

 

CardioFlux calcium transient analysis overview of analyzed parametersOverview of analyzed parameters

 

Direct acute drug effects, including interference with ion channels, pumps, exchangers and hormone receptors, or kinase-mediated signaling involved in regulation of the human cardiomyocyte action potential and heart rate control can be detected by monitoring [Ca2+ ] transients, which makes it a valuable tool in drug discovery and safety pharmacology assessment.

CardioFlux herg blocker astimezole induces calcium transient prolongation arrhythmia and beating arresthERG blocker astemizole induces Ca2+  transient prolongation, arrhythmia and beating arrest: Raw data plots (left); 13.7 nM compound induces Ca2+  prolongation, while arrhythmia occurs at 123 nM. Analyzed data for 90 % of peak width duration (PWD90) over time (right).

 

In the ongoing CiPA validation study, calcium transient measurements are one of three methods to assess pro-arrhythmic effects on a subset of blinded compounds in Cor.4U®  cardiomyocytes.
The CardioFlux assay has been validated with >75 compounds from a wide variety of compound classes.

 

 

CardioFlux assay provides robust information with a anumber of quantifiable parameters peak duration beating rate amplitudeThe CardioFlux assay provides robust infor-mation with a number of quantifiable parameters, including transient peak duration (PWD30, 50, 90, etc.), beating rate and amplitude. The heat map on the left demonstrates compounds clustered according to known mechanisms of action, e.g., astemizole- induced beating arrest preceded by changes in beating rate PWD, and AMP.

 

 

 

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