• Nanion Technologies: Smart Tools for Ion Channel Research

    Nanion Technologies: Smart Tools for Ion Channel Research

  • CardioExcyte 96 SOL: Pacing Cardiomyocytes with Light

    CardioExcyte 96 SOL: Pacing Cardiomyocytes with Light

  • SURFE²R 96SE: Label-free HTS Transporter Screening

    SURFE²R 96SE: Label-free HTS Transporter Screening

  • Bilayer recordings: Orbit product family

    Bilayer recordings: Orbit product family

Our Product Portfolio

SyncroPatch 384i

SyncroPatch 384i

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16

Orbit 16

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

2019 - Pharmacological enhancement of repolarization reserve in human induced pluripotent stem cells derived cardiomyocytes

Icon CE   CardioExcyte 96 publication in Biochem. Pharmacol. (2019)

Authors:
Treat JA, Goodrow RJ, Bot CT, Haedo RJ, Cordeiro JM.

Journal:
Biochem. Pharmacol. (2019) 169:113608


Abstract:

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used for many applications including safety pharmacology. However, a deficiency or complete absence of several K+ currents suggests repolarization reserve is low in hiPSC-CMs. We determined whether a dual Ito and IKr activator can improve repolarization reserve in hiPSC-CMs resulting in a more electrophysiologically mature phenotype.

METHODS AND RESULTS: Human iPSC were maintained on growth factor and differentiated into the cardiac phenotype by addition of selective Wnt molecules. Current and voltage clamp recordings in single cells were made using patch electrodes. Extracellular field potentials were made using a microelectrode array on hiPSC monolayers. Action potential recordings from hiPSC-CMs following application of an IKr inhibitor resulted in depolarization of the membrane potential and prolongation of the APD. A flattening of the T-wave was noted on the pseudo-ECG. In contrast, application of the IKr and Ito agonist, NS3623, resulted in hyperpolarization of the membrane, slowing of the spontaneous rate and shortening of the APD. Voltage clamp recording showed a significant increase in IKr; no enhancement of Ito in hiPSC-CMs was noted. AP clamp experiments revealed that IKr plays a role in both phase 3 repolarization and phase 4 depolarization. mRNA analysis revealed that KCNH2 is abundantly expressed in hiPSC-CM, consistent with electrophysiological recordings.

CONCLUSIONS: Although NS3623 is a dual Ito and IKr activator in ventricular myocytes, application of this compound to hiPSC-CMs enhanced only IKr and no effect on Ito was noted. Our results suggest IKr enhancement can improve repolarization reserve in this cell type. The disconnect between a dramatic increase in Ito in adult myocytes versus the lack of effect in hiPSC-CMs suggest that the translation of pharmacological effects in hiPSC-CM to adult myocytes should be viewed with caution.


Download here

Back to Overview

Nanion Corporate Blog

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.