論文

査読有り 国際誌
2019年

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.

Stem cells international
  • Tadashi Takaki
  • ,
  • Azusa Inagaki
  • ,
  • Kazuhisa Chonabayashi
  • ,
  • Keiji Inoue
  • ,
  • Kenji Miki
  • ,
  • Seiko Ohno
  • ,
  • Takeru Makiyama
  • ,
  • Minoru Horie
  • ,
  • Yoshinori Yoshida

2019
開始ページ
7532657
終了ページ
7532657
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1155/2019/7532657

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 (pvalue = 0.031). Cardiomyocyte monolayers constituted mostly of ventricular cells derived from LQT1-iPSCs showed prolonged AP duration (APD) (pvalue = 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.

リンク情報
DOI
https://doi.org/10.1155/2019/7532657
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30956674
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431403
ID情報
  • DOI : 10.1155/2019/7532657
  • ISSN : 1687-966X
  • PubMed ID : 30956674
  • PubMed Central 記事ID : PMC6431403

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