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Title: Optical Recording of Action Potentials in Human Induced Pluripotent Stem Cell-Derived Cardiac Single Cells and Monolayers Generated from Long QT Syndrome Type 1 Patients
Authors: Takaki, Tadashi
Inagaki, Azusa
Chonabayashi, Kazuhisa  kyouindb  KAKEN_id
Inoue, Keiji
Miki, Kenji
Ohno, Seiko
Makiyama, Takeru  kyouindb  KAKEN_id
Horie, Minoru
Yoshida, Yoshinori  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5511-9090 (unconfirmed)
Author's alias: 高木, 正
稲垣, 梓
蝶名林, 和久
井上, 啓司
三木, 健嗣
大野, 聖子
牧山, 武
堀江, 稔
吉田, 善紀
Issue Date: 6-Mar-2019
Publisher: Hindawi Limited
Journal title: Stem Cells International
Volume: 2019
Thesis number: 7532657
Abstract: Induced pluripotent stem cells (iPSCs) from type 1 long QT (LQT1) patients can differentiate into cardiomyocytes (CMs) including ventricular cells to recapitulate the disease phenotype. Although optical recordings using membrane potential dyes to monitor action potentials (APs) were reported, no study has investigated the disease phenotypes of cardiac channelopathy in association with the cardiac subtype at the single-cell level. We induced iPSC-CMs from three control and three LQT1 patients. Single-cell analysis using a fast-responding dye confirmed that ventricular cells were the dominant subtype (control-iPSC-CMs: 98%, 88%, 91%; LQT1-iPSC-CMs: 95%, 79%, 92%). In addition, LQT1-iPSC-ventricular cells displayed an increased frequency of early afterdepolarizations (p value = 0.031). Cardiomyocyte monolayers constituted mostly of ventricular cells derived from LQT1-iPSCs showed prolonged AP duration (APD) (p value = 0.000096). High-throughput assays using cardiomyocyte monolayers in 96-well plates demonstrated that IKr inhibitors prolonged APDs in both control- and LQT1-iPSC-CM monolayers. We confirmed that the optical recordings of APs in single cells and monolayers derived from control- and LQT1-iPSC-CMs can be used to assess arrhythmogenicity, supporting the feasibility of membrane potential dye-based high-throughput screening to study ventricular arrhythmias caused by genetic channelopathy or cardiotoxic drugs.
Rights: © 2019 Tadashi Takaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
URI: http://hdl.handle.net/2433/241627
DOI(Published Version): 10.1155/2019/7532657
PubMed ID: 30956674
Appears in Collections:Journal Articles

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