Electrophysiological properties of iPS cell-derived cardiomyocytes from a patient with long QT syndrome type 1 harboring the novel mutation M437V of KCNQ1

Tatsufumi Sogo, Kumi Morikawa, Yasutaka Kurata, Peili Li, Takafumi Ichinose, Shinsuke Yuasa, Daizou Nozaki, Junichiro Miake, Haruaki Ninomiya, Wataru Shimizu, Keiichi Fukuda, Kazuhiro Yamamoto, Yasuaki Shirayoshi, Ichiro Hisatome

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Introduction Long QT syndrome type 1 (LQT1) is caused by mutations in KCNQ1 coding slowly-activating delayed-rectifier K+ channels. We identified the novel missense mutation M437V of KCNQ1 in a LQT1 patient. Here, we employed iPS cell (iPSC)-derived cardiomyocytes to investigate electrophysiological properties of the mutant channel and LQT1 cardiomyocytes. Methods To generate iPSCs from the patient and a healthy subject, peripheral blood T cells were reprogrammed by Sendai virus vector encoding human OCT3/4, SOX2, KLF4, and c-MYC. Cardiomyocytes were prepared from iPSCs and human embryonic stem cells using a cytokine-based two-step differentiation method and were subjected to patch clamp experiments. Results LQT1 iPSC-derived cardiomyocytes exhibited prolongation of action potential duration (APD), which was due to a reduction of the KCNQ1-mediated current IKs; Na+, Ca2+ and other K+ channel currents were comparable. When expressed in HEK293 and COS7 cells, the mutant KCNQ1 was normally expressed in the plasma membrane but generated smaller currents than the wild type. Isoproterenol significantly prolonged APDs of LQT1 cardiomyocytes, while shortening those of healthy ones. A mathematical model for IKs-reduced human ventricular myocytes reproduced APD prolongation and generation of early afterdepolarizations (EADs) under β-adrenergic stimulation. Conclusions QT prolongation of the LQT1 patient with the mutation M437V of KCNQ1 was caused by IKs reduction, which may render the patient vulnerable to generation of EADs and arrhythmias.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalRegenerative Therapy
Publication statusPublished - 2016 Jun 1


  • C-terminus mutation
  • Early afterdepolarization
  • KCNQ1
  • LQT1
  • iPS cell

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Developmental Biology


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