Pharmacological Characterization of Human iPSC Cardiomyocytes Utilizing Manual Patch Clamp

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vCor.4U™ Ventricular Enriched Cardiomyocytes: Pharmacological Characterization Utilizing Manual Patch Clamp

Summary

Metrion Biosciences independent analysis of the spontaneous and pacing stability of vCor.4U^TM and their predictive response to selective pharmacological agents.

Extensive cardiac ion channel profiling at Metrion using selective pharmacological tools and manual patch clamp has enabled us to define the electrophysiological characteristics of vCor.4U^TM human iPSC-derived cardiomyocytes (iPSC-CM). vCor.4U^TM elicit spontaneous action potentials (AP) and can be paced at a range of frequencies (0.2 – 1 Hz).

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Extract

Overview

Extensive cardiac ion channel profiling at Metrion using selective pharmacological tools and manual patch clamp has enabled us to define the electrophysiological characteristics of vCor.4U^TM human iPSC-derived cardiomyocytes (iPSC-CM).

vCor.4U^TM elicit spontaneous action potentials (AP) and can be paced at a range of frequencies (0.2 – 1 Hz; Figure 1). The electrophysiological characteristics of evoked AP resemble primary human cardiomyocytes, with the cells having an average resting membrane potential of -73 mV and action potential duration at 90 % of repolarization (APD90) of 426 ms when paced at 1 Hz (Figure 1C).

vCor.4U^TM AP are stable over time in both spontaneous and evoked recording conditions confirming the suitability of vCor. 4U^TM for compound screening experiments (Figure 2). Additionally, we confirm that vCor.4U^TM express a predominantly ventricular phenotype and exhibit the appropriate pharmacology in response to core cardiac channel modulators, including early after depolarizations (EADs) following IKr inhibition (Figure 3).

In the light of the incoming CiPA guidelines, Axiogenesis vCor. 4U^TM iPSC-CM represent a suitable model for in vitro preclinical cardiac safety evaluation of compounds to identify potential human proarrhythmic liabilities.

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