IK1-enhanced Human-induced Pluripotent Stem Cell-derived Cardiomyocytes: an Improved Cardiomyocyte Model to Investigate Inherited Arrhythmia Syndromes

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2016 Apr 10

PMID 27059077

Citations 62

Authors

Ravi Vaidyanathan

Yogananda S Markandeya

Timothy J Kamp

Jonathan C Makielski

Craig T January

Lee L Eckhardt

Affiliations

Soon will be listed here.

Abstract

Currently available induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) do not ideally model cellular mechanisms of human arrhythmic disease due to lack of a mature action potential (AP) phenotype. In this study, we create and characterize iPS-CMs with an electrically mature AP induced by potassium inward rectifier (IK1) enhancement. The advantages of IK1-enhanced iPS-CMs include the absence of spontaneous beating, stable resting membrane potentials at approximately -80 mV and capability for electrical pacing. Compared with unenhanced, IK1-enhanced iPS-CMs calcium transient amplitudes were larger (P < 0.05) with a typical staircase pattern. IK1-enhanced iPS-CMs demonstrated a twofold increase in cell size and membrane capacitance and increased DNA synthesis compared with control iPS-CMs (P < 0.05). Furthermore, IK1-enhanced iPS-CMs expressing the F97C-CAV3 long QT9 mutation compared with wild-type CAV3 demonstrated an increase in AP duration and late sodium current. IK1-enhanced iPS-CMs represent a more mature cardiomyocyte model to study arrhythmia mechanisms.

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